Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection

SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, respon...

Full description

Saved in:
Bibliographic Details
Published inPLoS pathogens Vol. 17; no. 9; p. e1009878
Main Authors Severa, Martina, Diotti, Roberta A., Etna, Marilena P., Rizzo, Fabiana, Fiore, Stefano, Ricci, Daniela, Iannetta, Marco, Sinigaglia, Alessandro, Lodi, Alessandra, Mancini, Nicasio, Criscuolo, Elena, Clementi, Massimo, Andreoni, Massimo, Balducci, Stefano, Barzon, Luisa, Stefanelli, Paola, Clementi, Nicola, Coccia, Eliana M.
Format Journal Article
LanguageEnglish
Published San Francisco Public Library of Science 02.09.2021
Public Library of Science (PLoS)
Subjects
Antiviral agents
Antiviral drugs
Asymptomatic
Biology and life sciences
Carrier state (Communicable diseases)
Cell culture
Cell interaction
Cell surface
Chemokines
Coronaviruses
COVID-19
Cytokine storm
Cytokines
Dendritic cells
Development and progression
Disease
Epithelial cells
Epithelium
Experiments
Gene expression
Health aspects
Immune response
Immune system
Infections
Inflammation
Interferon
Ligands
Medicine and health sciences
Movement disorders
Neuropilin
PD-L1 protein
Peripheral blood mononuclear cells
Phenotypes
Pneumonia
Replication
Respiratory diseases
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
TLR7 protein
Toll-like receptors
Very Low Frequencies
Viral diseases
Viral infections
Viruses
Italy
Online AccessGet full text
ISSN1553-7374
1553-7366
1553-7374
DOI10.1371/journal.ppat.1009878

Cover

Abstract SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro , asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo . These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients.
AbstractList SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro, asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo. These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients.
SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro , asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo . These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients. SARS-CoV-2 pandemic has resulted in millions of infections and deaths worldwide, yet the role of host innate immune responses in COVID-19 pathogenesis remains only partially characterized. Innate immunity represents the first line of host defense against viruses. Upon viral recognition, the secretion of type I and III interferons (IFN) establishes the cellular state of viral resistance, and contributes to induce the specific adaptive immune responses. Moving from in vitro evidences on the protective role played by plasmacytoid dendritic cells (pDC)-released type I IFN in the early phase of SARS-CoV-2 infection, here we characterized ex vivo the pDC phenotype and the balance between anti-viral and pro-inflammatory cytokines of COVID-19 patients stratified according to disease severity. Our study confirms in COVID-19 the crucial and protective role of pDC/type I IFN axis, whose deeper understanding may contribute to the development of novel pharmacological strategies and/or host-directed therapies aimed at boosting pDC response since the early phases of SARS-CoV-2 infection.
SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro , asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo . These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients.
SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro, asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo. These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients.SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression. Indeed, critically ill patients show an impaired type I IFN response accompanied by elevated inflammatory cytokine and chemokine levels, responsible for cell and tissue damage and associated multi-organ failure. Here, the early interaction between SARS-CoV-2 and immune cells was investigated by interrogating an in vitro human peripheral blood mononuclear cell (PBMC)-based experimental model. We found that, even in absence of a productive viral replication, the virus mediates a vigorous TLR7/8-dependent production of both type I and III IFNs and inflammatory cytokines and chemokines, known to contribute to the cytokine storm observed in COVID-19. Interestingly, we observed how virus-induced type I IFN secreted by PBMC enhances anti-viral response in infected lung epithelial cells, thus, inhibiting viral replication. This type I IFN was released by plasmacytoid dendritic cells (pDC) via an ACE-2-indipendent but Neuropilin-1-dependent mechanism. Viral sensing regulates pDC phenotype by inducing cell surface expression of PD-L1 marker, a feature of type I IFN producing cells. Coherently to what observed in vitro, asymptomatic SARS-CoV-2 infected subjects displayed a similar pDC phenotype associated to a very high serum type I IFN level and induction of anti-viral IFN-stimulated genes in PBMC. Conversely, hospitalized patients with severe COVID-19 display very low frequency of circulating pDC with an inflammatory phenotype and high levels of chemokines and pro-inflammatory cytokines in serum. This study further shed light on the early events resulting from the interaction between SARS-CoV-2 and immune cells occurring in vitro and confirmed ex vivo. These observations can improve our understanding on the contribution of pDC/type I IFN axis in the regulation of the anti-viral state in asymptomatic and severe COVID-19 patients.
Audience Academic
Author Etna, Marilena P.
Criscuolo, Elena
Diotti, Roberta A.
Stefanelli, Paola
Iannetta, Marco
Mancini, Nicasio
Balducci, Stefano
Clementi, Massimo
Coccia, Eliana M.
Severa, Martina
Fiore, Stefano
Sinigaglia, Alessandro
Lodi, Alessandra
Clementi, Nicola
Rizzo, Fabiana
Barzon, Luisa
Ricci, Daniela
Andreoni, Massimo
AuthorAffiliation 1 Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
2 Laboratory of Medical Microbiology and Virology, Vita-Salute San Raffaele University, Milan, Italy
3 Infectious Disease Clinic, Policlinico Tor Vergata, Rome, Italy
4 Department of Molecular Medicine, University of Padova, Padua, Italy
5 Metabolic Fitness Association, Monterotondo, Rome, Italy
Washington University School of Medicine, UNITED STATES
AuthorAffiliation_xml – name: 3 Infectious Disease Clinic, Policlinico Tor Vergata, Rome, Italy
– name: 4 Department of Molecular Medicine, University of Padova, Padua, Italy
– name: 5 Metabolic Fitness Association, Monterotondo, Rome, Italy
– name: Washington University School of Medicine, UNITED STATES
– name: 2 Laboratory of Medical Microbiology and Virology, Vita-Salute San Raffaele University, Milan, Italy
– name: 1 Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy
Author_xml – sequence: 1
  givenname: Martina
  orcidid: 0000-0002-0411-4545
  surname: Severa
  fullname: Severa, Martina
– sequence: 2
  givenname: Roberta A.
  orcidid: 0000-0002-7853-3224
  surname: Diotti
  fullname: Diotti, Roberta A.
– sequence: 3
  givenname: Marilena P.
  orcidid: 0000-0003-2551-393X
  surname: Etna
  fullname: Etna, Marilena P.
– sequence: 4
  givenname: Fabiana
  orcidid: 0000-0001-9748-4571
  surname: Rizzo
  fullname: Rizzo, Fabiana
– sequence: 5
  givenname: Stefano
  orcidid: 0000-0002-2257-5492
  surname: Fiore
  fullname: Fiore, Stefano
– sequence: 6
  givenname: Daniela
  orcidid: 0000-0002-8445-512X
  surname: Ricci
  fullname: Ricci, Daniela
– sequence: 7
  givenname: Marco
  orcidid: 0000-0002-6938-8627
  surname: Iannetta
  fullname: Iannetta, Marco
– sequence: 8
  givenname: Alessandro
  surname: Sinigaglia
  fullname: Sinigaglia, Alessandro
– sequence: 9
  givenname: Alessandra
  orcidid: 0000-0001-7364-0381
  surname: Lodi
  fullname: Lodi, Alessandra
– sequence: 10
  givenname: Nicasio
  orcidid: 0000-0003-0637-0910
  surname: Mancini
  fullname: Mancini, Nicasio
– sequence: 11
  givenname: Elena
  orcidid: 0000-0003-0185-3147
  surname: Criscuolo
  fullname: Criscuolo, Elena
– sequence: 12
  givenname: Massimo
  surname: Clementi
  fullname: Clementi, Massimo
– sequence: 13
  givenname: Massimo
  surname: Andreoni
  fullname: Andreoni, Massimo
– sequence: 14
  givenname: Stefano
  orcidid: 0000-0001-8128-3863
  surname: Balducci
  fullname: Balducci, Stefano
– sequence: 15
  givenname: Luisa
  orcidid: 0000-0003-0720-8456
  surname: Barzon
  fullname: Barzon, Luisa
– sequence: 16
  givenname: Paola
  surname: Stefanelli
  fullname: Stefanelli, Paola
– sequence: 17
  givenname: Nicola
  surname: Clementi
  fullname: Clementi, Nicola
– sequence: 18
  givenname: Eliana M.
  orcidid: 0000-0002-1606-2949
  surname: Coccia
  fullname: Coccia, Eliana M.
BookMark eNqVkl2L1DAUhousuB_6DwQL3ujFjEmTtKkXwjLrR2Fxwa_bkCansxnapCaZxbnyr5vuVHGWRZAGGnKe9z05J-c0O7LOQpY9xWiJSYVfbdzWW9kvx1HGJUao5hV_kJ1gxsiiIhU9-mt_nJ2GsEGIYoLLR9kxobQiHLGT7OeF6TrwYKORfT72MgxS7aIzOtdgtTfRqFxBn2LXYF3cjZBLq_PbTZM3NoJPemdzD2F0NkBubC7DbhijG-SknvAANylJvrr61lwscJ2YDlQ0zj7OHnayD_Bk_p9lX9-9_bL6sLi8et-szi8XqkI0LhhSWHPG667jvOwUKwEXmnKlUxxLVUkCpGu5ajkuJaiS4EpyqilrC1bjgpxlz_a-Y--CmHsXRMF4WiWlE9HsCe3kRozeDNLvhJNG3B44vxbSp3p6EFITBDUUqlSMKt21bVGXvNaMSEQ7oMnrzZxt2w6gVWqvl_2B6WHEmmuxdjeCU1wUJU4GL2YD775vIUQxmDA9g7TgttO9y5pUFatIQp_fQe-vbqbWMhWQ2u9SXjWZivMyGaGa1ChRy3uo9GkYjErz15l0fiB4eSBITIQfcS23IYjm86f_YD8esnTPKu9C8ND96R1GYhr_30WKafzFPP5J9vqOTJkopzlLdZj-3-JfVRkO8Q
CitedBy_id crossref_primary_10_3389_fimmu_2021_797390
crossref_primary_10_5114_pq_182853
crossref_primary_10_1016_j_intimp_2023_109996
crossref_primary_10_1186_s12967_024_05044_7
crossref_primary_10_1016_j_bsheal_2023_08_005
crossref_primary_10_1016_j_isci_2024_109703
crossref_primary_10_1016_j_clim_2022_109177
crossref_primary_10_3389_fimmu_2022_1082912
crossref_primary_10_1016_j_coi_2022_01_003
crossref_primary_10_1016_j_cytogfr_2021_12_001
crossref_primary_10_1111_imr_13113
crossref_primary_10_1038_s41590_023_01545_7
crossref_primary_10_1146_annurev_immunol_090122_041105
crossref_primary_10_1016_j_immuni_2022_04_013
crossref_primary_10_1128_CMR_00094_21
crossref_primary_10_1016_j_celrep_2025_115413
crossref_primary_10_1038_s41423_024_01167_5
crossref_primary_10_1002_jmv_28000
crossref_primary_10_3389_fimmu_2023_1202197
crossref_primary_10_1038_s41392_025_02174_2
crossref_primary_10_3389_fimmu_2023_1244556
crossref_primary_10_1016_j_jinf_2023_01_019
crossref_primary_10_1186_s12929_022_00872_5
crossref_primary_10_1183_16000617_0250_2023
crossref_primary_10_1111_joim_13559
crossref_primary_10_3389_fimmu_2022_968991
crossref_primary_10_1007_s43440_022_00432_6
crossref_primary_10_1038_s41586_022_04447_0
crossref_primary_10_3389_fimmu_2024_1382655
crossref_primary_10_2174_0118715303265274231204075802
crossref_primary_10_15252_embj_2021109622
crossref_primary_10_1097_BS9_0000000000000132
crossref_primary_10_1016_j_isci_2023_107219
crossref_primary_10_3389_fimmu_2024_1502937
crossref_primary_10_1002_cti2_1434
crossref_primary_10_1038_s41423_023_01039_4
crossref_primary_10_3389_fimmu_2021_733171
crossref_primary_10_1016_j_jmb_2021_167438
crossref_primary_10_1128_jvi_01235_24
crossref_primary_10_1111_imcb_12615
crossref_primary_10_1126_sciimmunol_add4906
crossref_primary_10_1371_journal_pcbi_1009587
crossref_primary_10_1038_s41467_023_36140_9
crossref_primary_10_2217_fmb_2022_0103
crossref_primary_10_1016_j_celrep_2022_111148
crossref_primary_10_2174_0115733998294022240309105112
Cites_doi 10.1016/j.cell.2020.04.035
10.1126/science.abd2985
10.1016/S0140-6736(20)30628-0
10.1038/s41586-020-2601-5
10.1016/j.celrep.2020.108185
10.1136/bmj.m1443
10.1172/JCI140335
10.1080/22221751.2020.1780953
10.1016/S2213-2600(20)30076-X
10.1084/jem.20201387
10.1016/S0140-6736(20)30183-5
10.1038/s41586-020-2488-1
10.4049/jimmunol.162.6.3549
10.1016/j.antiviral.2020.104742
10.1073/pnas.0408506102
10.1371/journal.ppat.1008737
10.1128/JVI.03607-14
10.1016/j.chom.2020.04.004
10.1093/infdis/jiaa350
10.1182/blood-2006-05-023770
10.1177/1753466620933508
10.3389/fimmu.2021.627548
10.1101/cshperspect.a016303
10.1126/science.abd4570
10.1038/nature06116
10.1038/s41467-020-17665-9
10.1016/j.chom.2020.05.008
10.4049/jimmunol.171.10.5571
10.1016/j.immuni.2020.07.026
10.1371/journal.ppat.1009505
10.1038/s41556-021-00681-2
10.1016/j.cell.2020.04.026
10.1080/22221751.2021.1872354
10.1038/s41598-021-85425-w
10.4049/jimmunol.165.11.6037
10.1128/JVI.02935-13
10.1002/eji.201242552
10.1126/science.abc6027
10.1038/s41590-017-0012-z
10.1016/S2665-9913(20)30121-1
10.1016/S1473-3099(20)30484-9
10.1038/s41392-020-0211-1
10.3389/fimmu.2020.01441
10.1098/rsob.200160
10.1001/jama.2020.5394
10.1038/s41591-020-0901-9
10.1016/j.immuni.2019.03.025
10.1126/science.abc3545
10.1038/nri2358
10.1126/science.abb8925
10.1038/s41591-020-1038-6
10.1016/j.csbj.2021.01.034
10.1016/j.virusres.2020.198074
10.1038/s41577-020-0311-8
10.1096/fasebj.11.10.9271361
10.1016/j.chom.2020.05.009
ContentType Journal Article
Copyright COPYRIGHT 2021 Public Library of Science
2021 Severa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2021 Severa et al 2021 Severa et al
Copyright_xml – notice: COPYRIGHT 2021 Public Library of Science
– notice: 2021 Severa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
– notice: 2021 Severa et al 2021 Severa et al
DBID AAYXX
CITATION
ISN
ISR
3V.
7QL
7U9
7X7
7XB
88E
8FE
8FH
8FI
8FJ
8FK
ABUWG
AEUYN
AFKRA
AZQEC
BBNVY
BENPR
BHPHI
C1K
CCPQU
COVID
DWQXO
FYUFA
GHDGH
GNUQQ
H94
HCIFZ
K9.
LK8
M0S
M1P
M7P
PHGZM
PHGZT
PIMPY
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQQKQ
PQUKI
PRINS
7X8
5PM
DOA
DOI 10.1371/journal.ppat.1009878
DatabaseName CrossRef
Canada (Gale in Context)
Gale In Context: Science
ProQuest Central (Corporate)
Bacteriology Abstracts (Microbiology B)
Virology and AIDS Abstracts
Health & Medical Collection
ProQuest Central (purchase pre-March 2016)
Medical Database (Alumni Edition)
ProQuest SciTech Collection
ProQuest Natural Science Collection
Hospital Premium Collection
Hospital Premium Collection (Alumni Edition)
ProQuest Central (Alumni) (purchase pre-March 2016)
ProQuest Central (Alumni)
ProQuest One Sustainability (subscription)
ProQuest Central UK/Ireland
ProQuest Central Essentials
Biological Science Collection
ProQuest Central
Natural Science Collection
Environmental Sciences and Pollution Management
ProQuest One Community College
Coronavirus Research Database
ProQuest Central
Health Research Premium Collection
Health Research Premium Collection (Alumni)
ProQuest Central Student
AIDS and Cancer Research Abstracts
SciTech Premium Collection
ProQuest Health & Medical Complete (Alumni)
ProQuest Biological Science Collection
Health & Medical Collection (Alumni)
Medical Database
Biological Science Database
ProQuest Central Premium
ProQuest One Academic
Publicly Available Content Database
ProQuest Health & Medical Research Collection
ProQuest One Academic Middle East (New)
ProQuest One Health & Nursing
ProQuest One Academic Eastern Edition (DO NOT USE)
ProQuest One Applied & Life Sciences
ProQuest One Academic
ProQuest One Academic UKI Edition
ProQuest Central China
MEDLINE - Academic
PubMed Central (Full Participant titles)
Directory of Open Access Journals (DOAJ)
DatabaseTitle CrossRef
Publicly Available Content Database
ProQuest Central Student
ProQuest One Academic Middle East (New)
ProQuest Central Essentials
ProQuest Health & Medical Complete (Alumni)
ProQuest Central (Alumni Edition)
SciTech Premium Collection
ProQuest One Community College
ProQuest One Health & Nursing
ProQuest Natural Science Collection
ProQuest Central China
Environmental Sciences and Pollution Management
ProQuest Central
ProQuest One Applied & Life Sciences
ProQuest One Sustainability
ProQuest Health & Medical Research Collection
Health Research Premium Collection
Health and Medicine Complete (Alumni Edition)
Natural Science Collection
ProQuest Central Korea
Bacteriology Abstracts (Microbiology B)
Health & Medical Research Collection
Biological Science Collection
AIDS and Cancer Research Abstracts
ProQuest Central (New)
ProQuest Medical Library (Alumni)
Virology and AIDS Abstracts
ProQuest Biological Science Collection
ProQuest One Academic Eastern Edition
Coronavirus Research Database
ProQuest Hospital Collection
Health Research Premium Collection (Alumni)
Biological Science Database
ProQuest SciTech Collection
ProQuest Hospital Collection (Alumni)
ProQuest Health & Medical Complete
ProQuest Medical Library
ProQuest One Academic UKI Edition
ProQuest One Academic
ProQuest One Academic (New)
ProQuest Central (Alumni)
MEDLINE - Academic
DatabaseTitleList



Publicly Available Content Database
CrossRef
MEDLINE - Academic
Database_xml – sequence: 1
  dbid: DOA
  name: DOAJ Directory of Open Access Journals
  url: https://www.doaj.org/
  sourceTypes: Open Website
– sequence: 2
  dbid: BENPR
  name: ProQuest Central
  url: https://www.proquest.com/central
  sourceTypes: Aggregation Database
DeliveryMethod fulltext_linktorsrc
Discipline Biology
DocumentTitleAlternate Plasmacytoid dendritic cells and type I IFN in COVID-19
EISSN 1553-7374
ExternalDocumentID 2582586442
oai_doaj_org_article_ad30e9e2c6c54cdfbb29689d53a04fe4
PMC8412261
A677509390
10_1371_journal_ppat_1009878
GeographicLocations Italy
GeographicLocations_xml – name: Italy
GrantInformation_xml – fundername: ;
– fundername: ;
  grantid: 874735
– fundername: ;
  grantid: GR-2016-02363749
GroupedDBID ---
123
29O
2WC
53G
5VS
7X7
88E
8FE
8FH
8FI
8FJ
AAFWJ
AAUCC
AAWOE
AAYXX
ABDBF
ABUWG
ACGFO
ACIHN
ACPRK
ACUHS
ADBBV
AEAQA
AENEX
AEUYN
AFKRA
AFPKN
AFRAH
AHMBA
ALMA_UNASSIGNED_HOLDINGS
AOIJS
B0M
BAWUL
BBNVY
BCNDV
BENPR
BHPHI
BPHCQ
BVXVI
BWKFM
CCPQU
CITATION
CS3
DIK
DU5
E3Z
EAP
EAS
EBD
EMK
EMOBN
ESX
F5P
FPL
FYUFA
GROUPED_DOAJ
GX1
HCIFZ
HMCUK
HYE
IAO
IHR
INH
INR
ISN
ISR
ITC
KQ8
LK8
M1P
M48
M7P
MM.
O5R
O5S
OK1
OVT
P2P
PGMZT
PHGZM
PHGZT
PIMPY
PQQKQ
PROAC
PSQYO
PV9
QF4
QN7
RNS
RPM
RZL
SV3
TR2
TUS
UKHRP
WOW
~8M
PMFND
3V.
7QL
7U9
7XB
8FK
AZQEC
C1K
COVID
DWQXO
GNUQQ
H94
K9.
PJZUB
PKEHL
PPXIY
PQEST
PQGLB
PQUKI
PRINS
7X8
5PM
PUEGO
-
AAPBV
ABPTK
ADACO
BBAFP
M~E
ID FETCH-LOGICAL-c704t-50c1d8589ff886fc56e12d48cdc701ac7a3e3fb8cb816aec6317a84d45b259123
IEDL.DBID M48
ISSN 1553-7374
1553-7366
IngestDate Fri Nov 26 17:11:52 EST 2021
Wed Aug 27 01:31:39 EDT 2025
Thu Aug 21 18:20:48 EDT 2025
Fri Jul 11 03:52:02 EDT 2025
Fri Jul 25 12:02:53 EDT 2025
Tue Jun 17 21:36:37 EDT 2025
Tue Jun 10 20:38:40 EDT 2025
Fri Jun 27 04:21:58 EDT 2025
Fri Jun 27 04:50:08 EDT 2025
Tue Jul 01 01:14:02 EDT 2025
Thu Apr 24 22:53:14 EDT 2025
IsDoiOpenAccess true
IsOpenAccess true
IsPeerReviewed true
IsScholarly true
Issue 9
Language English
License This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Creative Commons Attribution License
LinkModel DirectLink
MergedId FETCHMERGED-LOGICAL-c704t-50c1d8589ff886fc56e12d48cdc701ac7a3e3fb8cb816aec6317a84d45b259123
Notes ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
These authors are joint senior authors on this work.
The authors have declared that no competing interests exist.
ORCID 0000-0002-0411-4545
0000-0002-2257-5492
0000-0002-7853-3224
0000-0003-2551-393X
0000-0003-0720-8456
0000-0003-0185-3147
0000-0002-8445-512X
0000-0002-6938-8627
0000-0002-1606-2949
0000-0001-8128-3863
0000-0001-7364-0381
0000-0001-9748-4571
0000-0003-0637-0910
OpenAccessLink http://journals.scholarsportal.info/openUrl.xqy?doi=10.1371/journal.ppat.1009878
PMID 34473805
PQID 2582586442
PQPubID 1436335
ParticipantIDs plos_journals_2582586442
doaj_primary_oai_doaj_org_article_ad30e9e2c6c54cdfbb29689d53a04fe4
pubmedcentral_primary_oai_pubmedcentral_nih_gov_8412261
proquest_miscellaneous_2569377573
proquest_journals_2582586442
gale_infotracmisc_A677509390
gale_infotracacademiconefile_A677509390
gale_incontextgauss_ISR_A677509390
gale_incontextgauss_ISN_A677509390
crossref_primary_10_1371_journal_ppat_1009878
crossref_citationtrail_10_1371_journal_ppat_1009878
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 20210902
PublicationDateYYYYMMDD 2021-09-02
PublicationDate_xml – month: 9
  year: 2021
  text: 20210902
  day: 2
PublicationDecade 2020
PublicationPlace San Francisco
PublicationPlace_xml – name: San Francisco
– name: San Francisco, CA USA
PublicationTitle PLoS pathogens
PublicationYear 2021
Publisher Public Library of Science
Public Library of Science (PLoS)
Publisher_xml – name: Public Library of Science
– name: Public Library of Science (PLoS)
References J.Y. Li (ppat.1009878.ref038) 2020; 286
P. Mehta (ppat.1009878.ref062) 2020; 395
C.L. Sokol (ppat.1009878.ref033) 2015; 7
A. Sauty (ppat.1009878.ref045) 1999; 162
Z. Xu (ppat.1009878.ref050) 2020; 8
A. Broggi (ppat.1009878.ref053) 2020; 369
C.G.K. Ziegler (ppat.1009878.ref027) 2020; 181
M.C. Pontelli (ppat.1009878.ref051)
C. Huang (ppat.1009878.ref001) 2020; 395
S. Pichyangkul (ppat.1009878.ref057) 2003; 171
J.B. Moore (ppat.1009878.ref042) 2020; 368
O. Byambasuren (ppat.1009878.ref005) 2020
A.A. Maghazachi (ppat.1009878.ref044) 1997; 11
M. Sa Ribero (ppat.1009878.ref035) 2020; 16
L.F. Garcia (ppat.1009878.ref041) 2020; 11
A.J. Combes (ppat.1009878.ref012) 2020
X. Lei (ppat.1009878.ref024) 2020; 11
X. Xie (ppat.1009878.ref058) 2020; 27
M.P. Etna (ppat.1009878.ref060) 2021; 17
S. Zheng (ppat.1009878.ref048) 2020; 369
N. Clementi (ppat.1009878.ref052) 2020; 222
H.M. Lazear (ppat.1009878.ref032) 2019; 50
L. Cervantes-Barragan (ppat.1009878.ref054) 2021
M. Gilliet (ppat.1009878.ref013) 2008; 8
I. Sanchez-Cerrillo (ppat.1009878.ref020) 2020; 130
B.A. Khalil (ppat.1009878.ref043) 2021; 19
E. Lavezzo (ppat.1009878.ref002) 2020; 584
A. Fara (ppat.1009878.ref063) 2020; 10
A.G. Laing (ppat.1009878.ref018) 2020.; 26
M. Severa (ppat.1009878.ref064) 2013; 43
C.K. Yuen (ppat.1009878.ref040) 2020; 9
S.G. Alculumbre (ppat.1009878.ref031) 2018; 19
A. Park (ppat.1009878.ref037) 2020; 27
M.Z. Tay (ppat.1009878.ref006) 2020; 20
A. Boumaza (ppat.1009878.ref028) 2021
Y. Konno (ppat.1009878.ref039) 2020; 32
C. Pelaia (ppat.1009878.ref049) 2020; 14
R. Zhou (ppat.1009878.ref017) 2020; 53
F. Onodi (ppat.1009878.ref055) 2021; 218
M. Liao (ppat.1009878.ref021) 2020; 26
A.K. Palucka (ppat.1009878.ref059) 2005; 102
J.S. Lee (ppat.1009878.ref008) 2020; 5
Z.S. Xu (ppat.1009878.ref046) 2020; 5
B. Coutard (ppat.1009878.ref056) 2020; 176
D. Blanco-Melo (ppat.1009878.ref022) 2020; 181
R. Lande (ppat.1009878.ref065) 2007; 449
L. Cantuti-Castelvetri (ppat.1009878.ref029) 2020; 370
M.A. Zingaropoli (ppat.1009878.ref019) 2021; 12
M. Biasin (ppat.1009878.ref026) 2021; 11
C.I. van der Made (ppat.1009878.ref010) 2020
J.L. McKechnie (ppat.1009878.ref023) 2020; 27
L. Cervantes-Barragan (ppat.1009878.ref014) 2007; 109
P. Bastard (ppat.1009878.ref011) 2020
V.A. Scheuplein (ppat.1009878.ref016) 2015; 89
G. Grasselli (ppat.1009878.ref047) 2020; 323
V.S. Raj (ppat.1009878.ref015) 2014; 88
E. Criscuolo (ppat.1009878.ref025) 2021; 10
D. Shin (ppat.1009878.ref036) 2020; 587
E. Petersen (ppat.1009878.ref034) 2020; 20
M. Saichi (ppat.1009878.ref061) 2021; 23
A. Dzionek (ppat.1009878.ref030) 2000; 165
J. Hadjadj (ppat.1009878.ref007) 2020; 369
Q. Ding (ppat.1009878.ref003) 2020
D. McGonagle (ppat.1009878.ref004) 2020; 2
Q. Zhang (ppat.1009878.ref009) 2020; 370
References_xml – volume: 181
  start-page: 1016
  issue: 5
  year: 2020
  ident: ppat.1009878.ref027
  article-title: SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues
  publication-title: Cell
  doi: 10.1016/j.cell.2020.04.035
– volume: 370
  start-page: 856
  issue: 6518
  year: 2020
  ident: ppat.1009878.ref029
  article-title: Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
  publication-title: Science
  doi: 10.1126/science.abd2985
– volume: 395
  start-page: 1033
  issue: 10229
  year: 2020
  ident: ppat.1009878.ref062
  article-title: COVID-19: consider cytokine storm syndromes and immunosuppression
  publication-title: Lancet
  doi: 10.1016/S0140-6736(20)30628-0
– volume: 587
  start-page: 657
  issue: 7835
  year: 2020
  ident: ppat.1009878.ref036
  article-title: Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity
  publication-title: Nature
  doi: 10.1038/s41586-020-2601-5
– volume: 32
  start-page: 108185
  issue: 12
  year: 2020
  ident: ppat.1009878.ref039
  article-title: SARS-CoV-2 ORF3b Is a Potent Interferon Antagonist Whose Activity Is Increased by a Naturally Occurring Elongation Variant
  publication-title: Cell Rep
  doi: 10.1016/j.celrep.2020.108185
– volume: 369
  start-page: m1443
  year: 2020
  ident: ppat.1009878.ref048
  article-title: Viral load dynamics and disease severity in patients infected with SARS-CoV-2 in Zhejiang province, China, January-March 2020: retrospective cohort study
  publication-title: BMJ
  doi: 10.1136/bmj.m1443
– volume: 130
  start-page: 6290
  issue: 12
  year: 2020
  ident: ppat.1009878.ref020
  article-title: COVID-19 severity associates with pulmonary redistribution of CD1c+ DCs and inflammatory transitional and nonclassical monocytes
  publication-title: J Clin Invest
  doi: 10.1172/JCI140335
– volume: 9
  start-page: 1418
  issue: 1
  year: 2020
  ident: ppat.1009878.ref040
  article-title: SARS-CoV-2 nsp13, nsp14, nsp15 and orf6 function as potent interferon antagonists
  publication-title: Emerg Microbes Infect
  doi: 10.1080/22221751.2020.1780953
– volume: 8
  start-page: 420
  issue: 4
  year: 2020
  ident: ppat.1009878.ref050
  article-title: Pathological findings of COVID-19 associated with acute respiratory distress syndrome
  publication-title: Lancet Respir Med
  doi: 10.1016/S2213-2600(20)30076-X
– volume: 218
  issue: 4
  year: 2021
  ident: ppat.1009878.ref055
  article-title: SARS-CoV-2 induces human plasmacytoid predendritic cell diversification via UNC93B and IRAK4
  publication-title: J Exp Med
  doi: 10.1084/jem.20201387
– volume: 395
  start-page: 497
  issue: 10223
  year: 2020
  ident: ppat.1009878.ref001
  article-title: Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
  publication-title: Lancet
  doi: 10.1016/S0140-6736(20)30183-5
– volume: 584
  start-page: 425
  issue: 7821
  year: 2020
  ident: ppat.1009878.ref002
  article-title: Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’
  publication-title: Nature
  doi: 10.1038/s41586-020-2488-1
– volume: 162
  start-page: 3549
  issue: 6
  year: 1999
  ident: ppat.1009878.ref045
  article-title: The T cell-specific CXC chemokines IP-10, Mig, and I-TAC are expressed by activated human bronchial epithelial cells
  publication-title: J Immunol
  doi: 10.4049/jimmunol.162.6.3549
– volume: 176
  start-page: 104742
  year: 2020
  ident: ppat.1009878.ref056
  article-title: The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade
  publication-title: Antiviral Res
  doi: 10.1016/j.antiviral.2020.104742
– volume: 102
  start-page: 3372
  issue: 9
  year: 2005
  ident: ppat.1009878.ref059
  article-title: Cross-regulation of TNF and IFN-alpha in autoimmune diseases
  publication-title: Proc Natl Acad Sci U S A
  doi: 10.1073/pnas.0408506102
– volume: 16
  start-page: e1008737
  issue: 7
  year: 2020
  ident: ppat.1009878.ref035
  article-title: Interplay between SARS-CoV-2 and the type I interferon response
  publication-title: PLoS Pathog
  doi: 10.1371/journal.ppat.1008737
– volume: 89
  start-page: 3859
  issue: 7
  year: 2015
  ident: ppat.1009878.ref016
  article-title: High secretion of interferons by human plasmacytoid dendritic cells upon recognition of Middle East respiratory syndrome coronavirus
  publication-title: J Virol
  doi: 10.1128/JVI.03607-14
– volume: 27
  start-page: 841
  issue: 5
  year: 2020
  ident: ppat.1009878.ref058
  article-title: An Infectious cDNA Clone of SARS-CoV-2
  publication-title: Cell Host Microbe
  doi: 10.1016/j.chom.2020.04.004
– volume: 222
  start-page: 722
  issue: 5
  year: 2020
  ident: ppat.1009878.ref052
  article-title: Interferon-beta-1a Inhibition of Severe Acute Respiratory Syndrome-Coronavirus 2 In Vitro When Administered After Virus Infection
  publication-title: J Infect Dis
  doi: 10.1093/infdis/jiaa350
– volume: 109
  start-page: 1131
  issue: 3
  year: 2007
  ident: ppat.1009878.ref014
  article-title: Control of coronavirus infection through plasmacytoid dendritic-cell-derived type I interferon
  publication-title: Blood
  doi: 10.1182/blood-2006-05-023770
– volume: 14
  start-page: 1753466620933508
  year: 2020
  ident: ppat.1009878.ref049
  article-title: Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications
  publication-title: Ther Adv Respir Dis
  doi: 10.1177/1753466620933508
– volume: 12
  start-page: 627548
  year: 2021
  ident: ppat.1009878.ref019
  article-title: Increased sCD163 and sCD14 Plasmatic Levels and Depletion of Peripheral Blood Pro-Inflammatory Monocytes, Myeloid and Plasmacytoid Dendritic Cells in Patients With Severe COVID-19 Pneumonia
  publication-title: Front Immunol,
  doi: 10.3389/fimmu.2021.627548
– volume: 7
  issue: 5
  year: 2015
  ident: ppat.1009878.ref033
  article-title: The chemokine system in innate immunity
  publication-title: Cold Spring Harb Perspect Biol
  doi: 10.1101/cshperspect.a016303
– volume: 370
  issue: 6515
  year: 2020
  ident: ppat.1009878.ref009
  article-title: Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
  publication-title: Science
  doi: 10.1126/science.abd4570
– volume: 449
  start-page: 564
  issue: 7162
  year: 2007
  ident: ppat.1009878.ref065
  article-title: Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide
  publication-title: Nature
  doi: 10.1038/nature06116
– volume: 11
  start-page: 3810
  issue: 1
  year: 2020
  ident: ppat.1009878.ref024
  article-title: Activation and evasion of type I interferon responses by SARS-CoV-2
  publication-title: Nat Commun
  doi: 10.1038/s41467-020-17665-9
– volume: 27
  start-page: 870
  issue: 6
  year: 2020
  ident: ppat.1009878.ref037
  article-title: Type I and Type III Interferons—Induction, Signaling, Evasion, and Application to Combat COVID-19
  publication-title: Cell Host Microbe
  doi: 10.1016/j.chom.2020.05.008
– volume: 171
  start-page: 5571
  issue: 10
  year: 2003
  ident: ppat.1009878.ref057
  article-title: A blunted blood plasmacytoid dendritic cell response to an acute systemic viral infection is associated with increased disease severity
  publication-title: J Immunol
  doi: 10.4049/jimmunol.171.10.5571
– year: 2021
  ident: ppat.1009878.ref054
  article-title: Plasmacytoid dendritic cells produce type I interferon and reduce viral replication in airway epithelial cells after SARS-CoV-2 infection
  publication-title: bioRxiv
– volume: 53
  start-page: 864
  issue: 4
  year: 2020
  ident: ppat.1009878.ref017
  article-title: Acute SARS-CoV-2 Infection Impairs Dendritic Cell and T Cell Responses
  publication-title: Immunity
  doi: 10.1016/j.immuni.2020.07.026
– year: 2020
  ident: ppat.1009878.ref003
  article-title: The clinical characteristics of pneumonia patients coinfected with 2019 novel coronavirus and influenza virus in Wuhan, China
  publication-title: J Med Virol
– year: 2020
  ident: ppat.1009878.ref005
  publication-title: Estimating the extent of asymptomatic COVID-19 and its potential for community transmission: Systematic review and meta-analysis JAMMI
– volume: 17
  start-page: e1009505
  issue: 4
  year: 2021
  ident: ppat.1009878.ref060
  article-title: Human plasmacytoid dendritic cells at the crossroad of type I interferon-regulated B cell differentiation and antiviral response to tick-borne encephalitis virus
  publication-title: PLoS Pathog
  doi: 10.1371/journal.ppat.1009505
– volume: 23
  start-page: 538
  issue: 5
  year: 2021
  ident: ppat.1009878.ref061
  article-title: Single-cell RNA sequencing of blood antigen-presenting cells in severe COVID-19 reveals multi-process defects in antiviral immunity
  publication-title: Nat Cell Biol
  doi: 10.1038/s41556-021-00681-2
– volume: 181
  start-page: 1036
  issue: 5
  year: 2020
  ident: ppat.1009878.ref022
  article-title: Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19
  publication-title: Cell
  doi: 10.1016/j.cell.2020.04.026
– volume: 10
  start-page: 206
  issue: 1
  year: 2021
  ident: ppat.1009878.ref025
  article-title: Fast inactivation of SARS-CoV-2 by UV-C and ozone exposure on different materials
  publication-title: Emerg Microbes Infect
  doi: 10.1080/22221751.2021.1872354
– volume: 11
  start-page: 6260
  issue: 1
  year: 2021
  ident: ppat.1009878.ref026
  article-title: UV-C irradiation is highly effective in inactivating SARS-CoV-2 replication
  publication-title: Sci Rep
  doi: 10.1038/s41598-021-85425-w
– volume: 165
  start-page: 6037
  issue: 11
  year: 2000
  ident: ppat.1009878.ref030
  article-title: BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood
  publication-title: J Immunol
  doi: 10.4049/jimmunol.165.11.6037
– volume: 88
  start-page: 1834
  issue: 3
  year: 2014
  ident: ppat.1009878.ref015
  article-title: Adenosine deaminase acts as a natural antagonist for dipeptidyl peptidase 4-mediated entry of the Middle East respiratory syndrome coronavirus
  publication-title: J Virol
  doi: 10.1128/JVI.02935-13
– volume: 43
  start-page: 147
  issue: 1
  year: 2013
  ident: ppat.1009878.ref064
  article-title: EBV stimulates TLR- and autophagy-dependent pathways and impairs maturation in plasmacytoid dendritic cells: implications for viral immune escape
  publication-title: Eur J Immunol
  doi: 10.1002/eji.201242552
– volume: 369
  start-page: 718
  issue: 6504
  year: 2020
  ident: ppat.1009878.ref007
  article-title: Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients
  publication-title: Science
  doi: 10.1126/science.abc6027
– volume: 19
  start-page: 63
  issue: 1
  year: 2018
  ident: ppat.1009878.ref031
  article-title: Diversification of human plasmacytoid predendritic cells in response to a single stimulus
  publication-title: Nat Immunol
  doi: 10.1038/s41590-017-0012-z
– volume: 2
  start-page: e437
  issue: 7
  year: 2020
  ident: ppat.1009878.ref004
  article-title: Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia
  publication-title: Lancet Rheumatol
  doi: 10.1016/S2665-9913(20)30121-1
– year: 2021
  ident: ppat.1009878.ref028
  article-title: Monocytes and macrophages, targets of SARS-CoV-2: the clue for Covid-19 immunoparalysis
  publication-title: J Infect Dis
– volume: 20
  start-page: e238
  issue: 9
  year: 2020
  ident: ppat.1009878.ref034
  article-title: Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics
  publication-title: Lancet Infect Dis
  doi: 10.1016/S1473-3099(20)30484-9
– ident: ppat.1009878.ref051
  article-title: Infection of human lymphomononuclear cells by SARS-CoV-2
  publication-title: bioRxiv 2020.
– volume: 5
  start-page: 100
  issue: 1
  year: 2020
  ident: ppat.1009878.ref046
  article-title: Temporal profiling of plasma cytokines, chemokines and growth factors from mild, severe and fatal COVID-19 patients
  publication-title: Signal Transduct Target Ther,
  doi: 10.1038/s41392-020-0211-1
– volume: 11
  start-page: 1441
  year: 2020
  ident: ppat.1009878.ref041
  article-title: Immune Response, Inflammation, and the Clinical Spectrum of COVID-19
  publication-title: Front Immunol
  doi: 10.3389/fimmu.2020.01441
– volume: 10
  start-page: 200160
  issue: 9
  year: 2020
  ident: ppat.1009878.ref063
  article-title: Cytokine storm and COVID-19: a chronicle of pro-inflammatory cytokines
  publication-title: Open Biol
  doi: 10.1098/rsob.200160
– volume: 323
  start-page: 1574
  issue: 16
  year: 2020
  ident: ppat.1009878.ref047
  article-title: Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy
  publication-title: JAMA
  doi: 10.1001/jama.2020.5394
– volume: 26
  start-page: 842
  issue: 6
  year: 2020
  ident: ppat.1009878.ref021
  article-title: Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19
  publication-title: Nat Med
  doi: 10.1038/s41591-020-0901-9
– volume: 50
  start-page: 907
  issue: 4
  year: 2019
  ident: ppat.1009878.ref032
  article-title: Shared and Distinct Functions of Type I and Type III Interferons
  publication-title: Immunity
  doi: 10.1016/j.immuni.2019.03.025
– volume: 369
  start-page: 706
  issue: 6504
  year: 2020
  ident: ppat.1009878.ref053
  article-title: Type III interferons disrupt the lung epithelial barrier upon viral recognition
  publication-title: Science
  doi: 10.1126/science.abc3545
– year: 2020
  ident: ppat.1009878.ref011
  article-title: Auto-antibodies against type I IFNs in patients with life-threatening COVID-19
  publication-title: Science
– volume: 8
  start-page: 594
  issue: 8
  year: 2008
  ident: ppat.1009878.ref013
  article-title: Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases
  publication-title: Nat Rev Immunol
  doi: 10.1038/nri2358
– volume: 368
  start-page: 473
  issue: 6490
  year: 2020
  ident: ppat.1009878.ref042
  article-title: Cytokine release syndrome in severe COVID-19
  publication-title: Science
  doi: 10.1126/science.abb8925
– year: 2020
  ident: ppat.1009878.ref012
  article-title: Global Absence and Targeting of Protective Immune States in Severe COVID-19.
  publication-title: Res Sq
– volume: 26
  start-page: 1623
  issue: 10
  year: 2020.
  ident: ppat.1009878.ref018
  article-title: A dynamic COVID-19 immune signature includes associations with poor prognosis
  publication-title: Nat Med
  doi: 10.1038/s41591-020-1038-6
– year: 2020
  ident: ppat.1009878.ref010
  article-title: Presence of Genetic Variants Among Young Men With Severe COVID-19
  publication-title: JAMA
– volume: 19
  start-page: 976
  year: 2021
  ident: ppat.1009878.ref043
  article-title: Chemokines and chemokine receptors during COVID-19 infection
  publication-title: Comput Struct Biotechnol J
  doi: 10.1016/j.csbj.2021.01.034
– volume: 286
  start-page: 198074
  year: 2020
  ident: ppat.1009878.ref038
  article-title: The ORF6, ORF8 and nucleocapsid proteins of SARS-CoV-2 inhibit type I interferon signaling pathway
  publication-title: Virus Res
  doi: 10.1016/j.virusres.2020.198074
– volume: 20
  start-page: 363
  issue: 6
  year: 2020
  ident: ppat.1009878.ref006
  article-title: The trinity of COVID-19: immunity, inflammation and intervention
  publication-title: Nat Rev Immunol
  doi: 10.1038/s41577-020-0311-8
– volume: 5
  issue: 49
  year: 2020
  ident: ppat.1009878.ref008
  article-title: Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19
  publication-title: Sci Immunol
– volume: 11
  start-page: 765
  issue: 10
  year: 1997
  ident: ppat.1009878.ref044
  article-title: Interferon-inducible protein-10 and lymphotactin induce the chemotaxis and mobilization of intracellular calcium in natural killer cells through pertussis toxin-sensitive and -insensitive heterotrimeric G-proteins
  publication-title: FASEB J
  doi: 10.1096/fasebj.11.10.9271361
– volume: 27
  start-page: 863
  issue: 6
  year: 2020
  ident: ppat.1009878.ref023
  article-title: The Innate Immune System: Fighting on the Front Lines or Fanning the Flames of COVID-19?
  publication-title: Cell Host Microbe
  doi: 10.1016/j.chom.2020.05.009
SSID ssj0041316
Score 2.5658884
Snippet SARS-CoV-2 fine-tunes the interferon (IFN)-induced antiviral responses, which play a key role in preventing coronavirus disease 2019 (COVID-19) progression....
SourceID plos
doaj
pubmedcentral
proquest
gale
crossref
SourceType Open Website
Open Access Repository
Aggregation Database
Enrichment Source
Index Database
StartPage e1009878
SubjectTerms Antiviral agents
Antiviral drugs
Asymptomatic
Biology and life sciences
Carrier state (Communicable diseases)
Cell culture
Cell interaction
Cell surface
Chemokines
Coronaviruses
COVID-19
Cytokine storm
Cytokines
Dendritic cells
Development and progression
Disease
Epithelial cells
Epithelium
Experiments
Gene expression
Health aspects
Immune response
Immune system
Infections
Inflammation
Interferon
Ligands
Medicine and health sciences
Movement disorders
Neuropilin
PD-L1 protein
Peripheral blood mononuclear cells
Phenotypes
Pneumonia
Replication
Respiratory diseases
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
TLR7 protein
Toll-like receptors
Very Low Frequencies
Viral diseases
Viral infections
Viruses
SummonAdditionalLinks – databaseName: Directory of Open Access Journals (DOAJ)
  dbid: DOA
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV1Lb9NAEF6hSEhcEE81ENCCkDiZ2t6nj6WlapAoElDUm7XeB42U2lbjHHLirzOztqNaAvXCLcqMnXhmdveb9ew3hLzjxlYuFyzJfWUTHrhITJAmgSwsZE4A5oiHwr6cy7ML_vlSXN5q9YU1YT09cG-4Q-NY6gufW2kFty5UVV5IXTjBTMqDj0ygsOaNyVQ_B8PMHJueYlOcRDEph0NzTGWHg48-tK1B-ugUkm49WZQid_9-hp6162YzgZ_T4slbq9HpI_JwgJH0qP_7j8k9Xz8h9_vGkrun5PfJ0PcExu-atoCQr43ddc3KUZhnXGxvQHHPnmKJV4P7sNTUjsYPSxq3CeH6pqY3fQ2tp6uams3uuu2aSPIa1WFVhR-hx19_Lk-SrKBjZVf9jFycfvpxfJYMrRYSq1LeJSK1mdNCFyFoLYMV0me549o6kGfGKsM8C5W2lc6k8VYC7DCaOy4qyJ9g9XtOZnVT-wNCwdqFYkUo8M7gcS2MMApggOFVFXg-J2y0dWkHHnJsh7Eu48s1BflIb8MSPVQOHpqTZH9V2_Nw3KH_Ed2410UW7fgFxFY5xFZ5V2zNyVsMghJ5MmosxPlltptNufx-Xh5JhViLFek_lb5NlN4PSqGBh7VmOPwAJkP-rYnmYqIJo91OxAcYkOMzb8pcQI6vAdWCYRdjkP5d_GYvxpticV3tmy3qSACpSig2J2oS3BPzTSX16iqSkWueAYLPXvwPe78kD3IsGcL3dfmCzLqbrX8FmK-rXsfh_Qd_hFeA
  priority: 102
  providerName: Directory of Open Access Journals
– databaseName: Health & Medical Collection
  dbid: 7X7
  link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwhR3LbtNAcAVBSFxQeamBghaExMnUj335hEpL1SBRJKAoN2u9jzZSaps4OeTUX2dmswlY4nGLMrO2PLPz3NkZQl4zbWqb8yLJXW0S5hlPtBc6gSjMZ5aDzxEuhX06F2cX7OOUT2PCrY9llVudGBS1bQ3myA9zDrGMAuudv-t-JDg1Ck9X4wiN2-QOti7Dki453QVcoJ_D6FMcjZPIQoh4da6Q2WHk1Nuu09hEOoXQWw1MU-jgv9PTo27e9gMndFhC-ZtNOt0j96MzSY823H9AbrnmIbm7GS-5fkRuTuL0E5DiOe3AT77WZr1sZ5aCtrFhyAHFzD3FQq8Ws7FUN5aGHxMakoWwvm3oYlNJ6-isobpfX3fLNrR6DehgW-El9Pjz98lJkpV0W9_VPCYXpx--HZ8lceBCYmTKlglPTWYVV6X3SglvuHBZbpkyFuCZNlIXrvC1MrXKhHZGgPOhFbOM1xBFgQ18QkZN27h9QoHapSxKX-KTge-Ka64lOAOa1bVn-ZgUW1pXJnYjx6EY8yocsUmISjY0rJBDVeTQmCS7Vd2mG8d_8N8jG3e42Es7_NEuLqsompW2RepKlxthODPW13VeClVaXuiUecfG5BVuggq7ZTRYjnOpV31fTb6eV0dCosdVlOlfkb4MkN5EJN_Cxxodr0AAybAL1wDzYIAJMm8G4H3ckNtv7qtf0gErt5v0z-CXOzA-FEvsGteuEEeAqyq5LMZEDjb3gHxDSDO7Ci3JFcvAj8-e_vvlz8i9HEuC8DwuPyCj5WLlnoNPt6xfBMH9CWbMTc0
  priority: 102
  providerName: ProQuest
Title Differential plasmacytoid dendritic cell phenotype and type I Interferon response in asymptomatic and severe COVID-19 infection
URI https://www.proquest.com/docview/2582586442
https://www.proquest.com/docview/2569377573
https://pubmed.ncbi.nlm.nih.gov/PMC8412261
https://doaj.org/article/ad30e9e2c6c54cdfbb29689d53a04fe4
http://dx.doi.org/10.1371/journal.ppat.1009878
Volume 17
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwjV1Li9swEBa7WQq9lD7ZtGlQS6EnL37o5UMp-2RT2LRsm5KbkfXYBrK2GzvQnPrXO1LsUMMu7c1YIxmPZjTfSKMZhN4RqXId0ySITa4CYgkNpGUyAC_MRpoC5vCXwq6m7HJGPs3pfA91NVtbBtZ3unauntRstTz69XPzERT-g6_awKOu01FVSZcQOgQ3WuyjA7BN3KnqFdmdK8CK7YuhumI5AU84aS_T3TdKz1j5nP67lXtQLcu6B0v7QZV_WamLx-hRCy_x8VYenqA9UzxFD7YFJzfP0O-zth4K6PUSV4Ccb6XaNOVCY1h_tC97gN1ePnahX6Xbn8Wy0Ng_TLDfPoT-ZYFX29hagxcFlvXmtmpKn_zVk4O1hY_g08_fJ2dBlOIu4qt4jmYX599OL4O2BEOgeEiagIYq0oKK1FohmFWUmSjWRCgN7ZFUXCYmsblQuYiYNIoBHJGCaEJz8KvAKr5Ag6IszCHCCWMpT1KbupFBEgSVVHKAB5LkuSXxECUdrzPV5id3ZTKWmT904-CnbHmYuRnK2hkaomDXq9rm5_gH_Ymbxh2ty67tX5Srm6xV1kzqJDSpiRVTlCht8zxOmUg1TWRIrCFD9NYJQebyZxQuQOdGrus6m3ydZseMOwyWpOG9RNc9ovctkS3hZ5VsL0UAy1xerh7lqEcJq4DqNR86gez-uc5iCr6_ALQLjB11Qnp385tdsxvUBd0Vplw7GgbglVOeDBHvCXePff2WYvHDJykXJAJkH738j9FfoYexixRyx3TxCA2a1dq8BqjX5GO0z-d8jA5Ozqdfrsd-w2TsNfoPO9hZLA
linkProvider Scholars Portal
linkToHtml http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1Lb9QwELaqrRBcEE91oYBBIE6hiWMnzgGhtttql7YLKi3qLXVsp6y0TcJmK7Qn_hG_kRlvshCJx6m3KB4nysxkHvZ4PkJecqUzw0ToMZtpj-dceCqPlAdZWB4YATGHOxR2NI6Gp_z9mThbIz_aszBYVtnaRGeoTalxjXyLCchlJHhv9q766iFqFO6uthAaS7U4sItvkLLVb0cDkO8rxvb3TnaHXoMq4OnY53NP-DowUsgkz6WMci0iGzDDpTYwHigdq9CGeSZ1JoNIWR2Bh1WSGy4ySBUCbHQAJn-dh5DK9Mj6zt7443Fr-8EjOLBVBOPx4jCKmsN6YRxsNbrxpqoUtq32IdmXHWfoMANWnqFXTcu6E_Z2izZ_84L7d8jtJnyl20t9u0vWbHGP3FgCWi7uk--DBm8F7MaUVhCZXyq9mJcTQ8G-GQerQHGvgGJpWYnrv1QVhrqLEXXLkzC_LOhsWbtr6aSgql5cVvPSNZd15ODN4SV098Pn0cALEtpWlBUPyOm1COMh6RVlYTcIBW4ncZjkCT4ZNE0KJVQM4YfiWZZz1idhy-tUN_3PEYZjmrpNvRjyoCUPU5RQ2kioT7zVrGrZ_-M_9DsoxhUtdu92N8rZRdoYg1SZ0LeJZTrSgmuTZxlLIpkYESqf55b3yQtUghT7cxRYAHShruo6HX0ap9tRjDFemPh_JTruEL1uiPISPlar5tAFsAz7fnUoNzuUYGV0Z3gDFbL95jr99T_CzFZJ_zz8fDWMD8WivsKWV0gTQXAcizjsk7ij3B32dUeKyRfXBF3yADKH4NG_X_6M3ByeHB2mh6PxwWNyi2FBEu4Gsk3Sm8-u7BOIKOfZ0-Y3puT8ui3HT1U7jEQ
linkToPdf http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtR3LjtMw0FoVgbggntrCAgaBOIVtEjt2DggtW6otCwUBi3oLjh9LpW4SmlaoJ_6Lr2PGTQqReJz2FmXGiTwznoc9niHkEVM6NxGPg8jmOmCO8UC5RAUQhbnQcPA5_KWwN5Pk6IS9mvLpDvnR3oXBtMpWJ3pFbUqNe-T7EYdYRoL1jvZdkxbxbjh6Xn0NsIMUnrS27TQ2InJs198gfKufjYfA68dRNHr58fAoaDoMBFoM2DLgAx0ayWXqnJSJ0zyxYWSY1AbgodJCxTZ2udS5DBNldQLWVklmGM8hbAix6AGo_wsihknBWhLTbbAHtsG3XcW2PIGIk6S5theLcL-RkqdVpbCA9QDCftkxi757wNZG9Kp5WXcc4G765m_2cHSVXGkcWXqwkbxrZMcW18nFTWvL9Q3yfdh0XgENMqcV-OhnSq-X5cxQ0HTGN1igeGpAMcmsxJ1gqgpD_cOY-o1KGF8WdLHJ4rV0VlBVr8-qZenLzHp0sOvwE3r49tN4GIQpbXPLipvk5FxYcYv0irKwu4QCtVMRpy7FL4PMSa64EuCIKJbnjkV9Ere0znRTCR0bcswzf7wnICLa0DBDDmUNh_ok2I6qNpVA_oP_Atm4xcU63v5FuTjNGrWQKRMPbGojnWjOtHF5HqWJTA2P1YA5y_rkIQpBhpU6CpT5U7Wq62z8YZIdJAK9vTgd_BXpfQfpSYPkSpisVs31CyAZVgDrYO51MEHf6A54FwWynXOd_VqZMLIV0j-DH2zB-FFM7ytsuUKcBNxkwUXcJ6Ij3B3ydSHF7Isvhy5ZCDFEePvfP79PLoG-yF6PJ8d3yOUIM5PwWDDaI73lYmXvgmu5zO_5NUzJ5_NWGj8BHeCPFA
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Differential+plasmacytoid+dendritic+cell+phenotype+and+type+I+Interferon+response+in+asymptomatic+and+severe+COVID-19+infection&rft.jtitle=PLoS+pathogens&rft.au=Severa%2C+Martina&rft.au=Diotti%2C+Roberta+A&rft.au=Etna%2C+Marilena+P&rft.au=Rizzo%2C+Fabiana&rft.date=2021-09-02&rft.issn=1553-7374&rft.eissn=1553-7374&rft.volume=17&rft.issue=9&rft.spage=e1009878&rft_id=info:doi/10.1371%2Fjournal.ppat.1009878&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1553-7374&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1553-7374&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1553-7374&client=summon