Using Expanded Natural Killer Cells as Therapy for Invasive Aspergillosis
Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. Th...
Saved in:
| Published in | Journal of fungi (Basel) Vol. 6; no. 4; p. 231 |
|---|---|
| Main Authors | , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
MDPI
17.10.2020
MDPI AG |
| Subjects | |
| Online Access | Get full text |
Cover
Loading…
| Abstract | Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. This raises the consideration for immunotherapy as an adjunctive treatment. In this study, we evaluated the utility of expanded human NK cells as treatment against Aspergillus fumigatus infection in vitro and in vivo. The NK cells were expanded and activated by K562 cells genetically modified to express 4-1BB ligand and membrane-bound interleukin-15 (K562-41BBL-mbIL-15) as feeders. The efficacy of these cells was investigated in A. fumigatus killing assays in vitro and as adoptive cellular therapy in vivo. The expanded NK cells possessed potent killing activity at low effector-to-target ratio of 2:1. Fungicidal activity was morphotypal-dependent and most efficacious against A. fumigatus conidia. Fungicidal activity was mediated by dectin-1 receptors on the expanded NK cells leading to augmented release of perforin, resulting in enhanced direct cytolysis. In an immunocompromised mice pulmonary aspergillosis model, we showed that NK cell treatment significantly reduced fungal burden, hence demonstrating the translational potential of expanded NK cells as adjunctive therapy against IA in immunocompromised patients. |
|---|---|
| AbstractList | Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. This raises the consideration for immunotherapy as an adjunctive treatment. In this study, we evaluated the utility of expanded human NK cells as treatment against
Aspergillus fumigatus
infection in vitro and in vivo. The NK cells were expanded and activated by K562 cells genetically modified to express 4-1BB ligand and membrane-bound interleukin-15 (K562-41BBL-mbIL-15) as feeders. The efficacy of these cells was investigated in
A. fumigatus
killing assays in vitro and as adoptive cellular therapy in vivo. The expanded NK cells possessed potent killing activity at low effector-to-target ratio of 2:1. Fungicidal activity was morphotypal-dependent and most efficacious against
A. fumigatus
conidia. Fungicidal activity was mediated by dectin-1 receptors on the expanded NK cells leading to augmented release of perforin, resulting in enhanced direct cytolysis. In an immunocompromised mice pulmonary aspergillosis model, we showed that NK cell treatment significantly reduced fungal burden, hence demonstrating the translational potential of expanded NK cells as adjunctive therapy against IA in immunocompromised patients. Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high despite anti-fungal treatment, as the compromised status of immune system prevents the host from responding optimally to conventional therapy. This raises the consideration for immunotherapy as an adjunctive treatment. In this study, we evaluated the utility of expanded human NK cells as treatment against Aspergillus fumigatus infection in vitro and in vivo. The NK cells were expanded and activated by K562 cells genetically modified to express 4-1BB ligand and membrane-bound interleukin-15 (K562-41BBL-mbIL-15) as feeders. The efficacy of these cells was investigated in A. fumigatus killing assays in vitro and as adoptive cellular therapy in vivo. The expanded NK cells possessed potent killing activity at low effector-to-target ratio of 2:1. Fungicidal activity was morphotypal-dependent and most efficacious against A. fumigatus conidia. Fungicidal activity was mediated by dectin-1 receptors on the expanded NK cells leading to augmented release of perforin, resulting in enhanced direct cytolysis. In an immunocompromised mice pulmonary aspergillosis model, we showed that NK cell treatment significantly reduced fungal burden, hence demonstrating the translational potential of expanded NK cells as adjunctive therapy against IA in immunocompromised patients. |
| Author | Soe, Win Mar Williams, David L. Lee, Soo Chin Chotirmall, Sanjay H. Tan, Zhaohong Lim, Joan Hui Juan Chai, Louis Yi Ann Ali, Nur A’tikah Binte Mohamed Goh, Jessamine Geraldine Ravikumar, Sharada Seet, Ju Ee Sam, Qi Hui |
| AuthorAffiliation | 3 Department of Surgery and Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA; williamd@mail.etsu.edu 4 Department of Biochemistry, National University of Singapore, Singapore117596, Singapore; qihui.sam@nus.edu.sg 2 Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore 119074, Singapore; mdcleesc@nus.edu.sg 7 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore 1 Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore 119228, Singapore; winmarsoe18@gmail.com (W.M.S.); valdemar25@hotmail.com (J.H.J.L.); jessamine_goh@sris.a-star.edu.sg (J.G.G.); Zhaohong_tan@nuhs.edu.sg (Z.T.); sharada_ravikumar@nuhs.edu.sg (S.R.) 5 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 63 |
| AuthorAffiliation_xml | – name: 6 Department of Pathology, National University of Singapore, Singapore 117597, Singapore; ju_ee_seet@nuhs.edu.sg – name: 1 Division of Infectious Diseases, University Medicine Cluster, National University Health System, Singapore 119228, Singapore; winmarsoe18@gmail.com (W.M.S.); valdemar25@hotmail.com (J.H.J.L.); jessamine_goh@sris.a-star.edu.sg (J.G.G.); Zhaohong_tan@nuhs.edu.sg (Z.T.); sharada_ravikumar@nuhs.edu.sg (S.R.) – name: 3 Department of Surgery and Center for Inflammation, Infectious Disease and Immunity, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA; williamd@mail.etsu.edu – name: 4 Department of Biochemistry, National University of Singapore, Singapore117596, Singapore; qihui.sam@nus.edu.sg – name: 7 Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore – name: 2 Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore 119074, Singapore; mdcleesc@nus.edu.sg – name: 5 Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 639798, Singapore; schotirmall@ntu.edu.sg (S.H.C.); atikah@ntu.edu.sg (N.A.B.M.A.) |
| Author_xml | – sequence: 1 givenname: Win Mar surname: Soe fullname: Soe, Win Mar – sequence: 2 givenname: Joan Hui Juan surname: Lim fullname: Lim, Joan Hui Juan – sequence: 3 givenname: David L. surname: Williams fullname: Williams, David L. – sequence: 4 givenname: Jessamine Geraldine surname: Goh fullname: Goh, Jessamine Geraldine – sequence: 5 givenname: Zhaohong surname: Tan fullname: Tan, Zhaohong – sequence: 6 givenname: Qi Hui orcidid: 0000-0002-8450-8519 surname: Sam fullname: Sam, Qi Hui – sequence: 7 givenname: Sanjay H. orcidid: 0000-0003-0417-7607 surname: Chotirmall fullname: Chotirmall, Sanjay H. – sequence: 8 givenname: Nur A’tikah Binte Mohamed surname: Ali fullname: Ali, Nur A’tikah Binte Mohamed – sequence: 9 givenname: Soo Chin surname: Lee fullname: Lee, Soo Chin – sequence: 10 givenname: Ju Ee surname: Seet fullname: Seet, Ju Ee – sequence: 11 givenname: Sharada surname: Ravikumar fullname: Ravikumar, Sharada – sequence: 12 givenname: Louis Yi Ann orcidid: 0000-0002-9640-0791 surname: Chai fullname: Chai, Louis Yi Ann |
| BookMark | eNpVkU1PGzEQhq0KVCjl0l_gI6oUOv5Y7_qChCIoUVG5JBI3y5_B0Wa9tTcR_Pu6BLXlNKOZV8-8M_MJHQ1p8Ah9IXDJmIRvmxQEcKCMfECnlIGcCegej_7LT9B5KRsAIE0npGQf0Qlj0EFHxSlarEoc1vjmedSD8w7_1NMu6x7_iH3vM577vi9YF7x88lmPLzikjBfDXpe49_i6jD6vqzKVWD6j46D74s_f4hla3d4s53ez-4fvi_n1_cxySqaZIUF764wW1nSiJdbI6l5KyoTgAowBHwLzjMrOWGEIZ8xyB8GFVtoAhJ2hxYHrkt6oMcetzi8q6aheCymvlc5TtL1XrXOmocBIZ4GTtjHAmuqCOsmlI22orKsDa9yZrXfWD1Nd_h30fWeIT2qd9qptSTVMK-DiDZDTr50vk9rGYuvR9ODTrijKm7oI7ziv0q8Hqc2plOzD3zEE1J9Xqn-vZL8BVPGRyw |
| CitedBy_id | crossref_primary_10_1007_s11046_022_00683_0 crossref_primary_10_3390_jof7020144 crossref_primary_10_3389_fimmu_2022_1044946 crossref_primary_10_1186_s11658_022_00363_3 crossref_primary_10_3390_jof7060451 crossref_primary_10_3389_fimmu_2022_1080822 crossref_primary_10_1128_spectrum_03614_23 crossref_primary_10_2147_JIR_S301784 |
| Cites_doi | 10.1016/j.chom.2013.09.007 10.4049/jimmunol.169.7.3876 10.2174/1381612811319200010 10.18632/oncotarget.12616 10.1093/jac/dkq437 10.1182/blood.V114.22.1640.1640 10.1038/s41598-017-06238-4 10.1093/infdis/jiq062 10.1128/mBio.01823-15 10.1086/589304 10.1016/j.jinf.2012.08.003 10.3389/fmicb.2015.01322 10.4049/jimmunol.1003593 10.3343/kjlm.2009.29.2.89 10.1016/j.micinf.2010.10.005 10.1158/1078-0432.CCR-10-0735 10.4049/jimmunol.0803462 10.1158/2326-6066.CIR-15-0229 10.7554/eLife.04177 10.4049/jimmunol.162.3.1633 10.1016/j.imbio.2015.01.002 10.1128/IAI.01455-08 10.5114/ceji.2014.42135 10.1128/CVI.00606-12 10.1007/s00262-016-1792-y 10.3324/haematol.2011.056747 10.1111/myc.12052 10.3389/fimmu.2016.00692 10.1038/nri1745 10.1371/journal.pone.0013418 10.1080/14653240310004548 10.1038/icb.1996.57 10.1158/0008-5472.CAN-08-3712 10.1056/NEJMoa020191 |
| ContentType | Journal Article |
| Copyright | 2020 by the authors. 2020 |
| Copyright_xml | – notice: 2020 by the authors. 2020 |
| DBID | AAYXX CITATION 7X8 5PM DOA |
| DOI | 10.3390/jof6040231 |
| DatabaseName | CrossRef MEDLINE - Academic PubMed Central (Full Participant titles) Directory of Open Access Journals |
| DatabaseTitle | CrossRef MEDLINE - Academic |
| DatabaseTitleList | CrossRef |
| Database_xml | – sequence: 1 dbid: DOA name: DOAJ Directory of Open Access Journals url: https://www.doaj.org/ sourceTypes: Open Website |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Botany |
| EISSN | 2309-608X |
| ExternalDocumentID | oai_doaj_org_article_7ddb520318c04175b035c422d949d17f 10_3390_jof6040231 |
| GroupedDBID | 53G 5VS 8FE 8FH AADQD AAFWJ AAHBH AAYXX ABDBF ADBBV AFKRA AFZYC ALMA_UNASSIGNED_HOLDINGS AOIJS BBNVY BCNDV BENPR BHPHI CCPQU CITATION GROUPED_DOAJ HCIFZ HYE IAO ITC KQ8 LK8 M7P MODMG M~E OK1 OZF PGMZT PIMPY PROAC RPM 7X8 5PM AFPKN |
| ID | FETCH-LOGICAL-c421t-b1faecdba6cb8671cb9402992366460bb0eff3e3298bc6b1433c4d0fdf79cf013 |
| IEDL.DBID | RPM |
| ISSN | 2309-608X |
| IngestDate | Tue Oct 22 15:13:57 EDT 2024 Tue Sep 17 21:18:22 EDT 2024 Fri Oct 25 00:28:06 EDT 2024 Fri Dec 06 09:21:29 EST 2024 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 4 |
| Language | English |
| License | https://creativecommons.org/licenses/by/4.0 Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c421t-b1faecdba6cb8671cb9402992366460bb0eff3e3298bc6b1433c4d0fdf79cf013 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0003-0417-7607 0000-0002-9640-0791 0000-0002-8450-8519 |
| OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712362/ |
| PMID | 33080826 |
| PQID | 2452984844 |
| PQPubID | 23479 |
| ParticipantIDs | doaj_primary_oai_doaj_org_article_7ddb520318c04175b035c422d949d17f pubmedcentral_primary_oai_pubmedcentral_nih_gov_7712362 proquest_miscellaneous_2452984844 crossref_primary_10_3390_jof6040231 |
| PublicationCentury | 2000 |
| PublicationDate | 20201017 |
| PublicationDateYYYYMMDD | 2020-10-17 |
| PublicationDate_xml | – month: 10 year: 2020 text: 20201017 day: 17 |
| PublicationDecade | 2020 |
| PublicationTitle | Journal of fungi (Basel) |
| PublicationYear | 2020 |
| Publisher | MDPI MDPI AG |
| Publisher_xml | – name: MDPI – name: MDPI AG |
| References | Schneider (ref_26) 2016; 7 Li (ref_21) 2013; 14 Herbrecht (ref_27) 2002; 347 Sutton (ref_25) 1996; 74 Schmidt (ref_9) 2011; 203 Park (ref_23) 2009; 182 ref_35 Pagano (ref_36) 2010; 66 Klingemann (ref_19) 2004; 6 Cho (ref_37) 2010; 16 Becker (ref_34) 2016; 7 Brown (ref_28) 2005; 6 Taylor (ref_29) 2002; 169 Steinbach (ref_1) 2012; 65 Roilides (ref_2) 2013; 56 Popko (ref_17) 2014; 1 Becker (ref_11) 2016; 65 Ziegler (ref_7) 2017; 7 Ravikumar (ref_3) 2015; 6 Marx (ref_15) 2014; 53 Ogbomo (ref_24) 2017; 7 Chai (ref_33) 2011; 13 Bouzani (ref_8) 2009; 114 Bouzani (ref_4) 2011; 187 Bouzani (ref_6) 2015; 54 Cho (ref_12) 2009; 29 Chai (ref_14) 2009; 77 Hohl (ref_31) 2008; 198 Schmidt (ref_5) 2013; 20 Kamiya (ref_13) 2016; 4 Fujisaki (ref_20) 2009; 69 Lehrnbecher (ref_10) 2013; 19 Dubey (ref_32) 2015; 220 Mehrad (ref_16) 1999; 162 Garg (ref_22) 2012; 97 Djeu (ref_18) 2002; 8 Chiba (ref_30) 2014; 3 |
| References_xml | – volume: 14 start-page: 387 year: 2013 ident: ref_21 article-title: The NK Receptor NKp30 Mediates Direct Fungal Recognition and Killing and Is Diminished in NK Cells from HIV-Infected Patients publication-title: Cell Host Microbe doi: 10.1016/j.chom.2013.09.007 contributor: fullname: Li – volume: 169 start-page: 3876 year: 2002 ident: ref_29 article-title: The β-Glucan Receptor, Dectin-1, Is Predominantly Expressed on the Surface of Cells of the Monocyte/Macrophage and Neutrophil Lineages publication-title: J. Immunol. doi: 10.4049/jimmunol.169.7.3876 contributor: fullname: Taylor – volume: 19 start-page: 3689 year: 2013 ident: ref_10 article-title: Immunotherapy in invasive fungal infection--focus on invasive aspergillosis publication-title: Curr. Pharm. Des. doi: 10.2174/1381612811319200010 contributor: fullname: Lehrnbecher – volume: 53 start-page: 301 year: 2014 ident: ref_15 article-title: Antibiotic Administration in the Drinking Water of Mice publication-title: J. Am. Assoc. Lab. Anim. Sci. contributor: fullname: Marx – volume: 7 start-page: 71062 year: 2016 ident: ref_26 article-title: Aspergillus fumigatus responds to natural killer (NK) cells with upregulation of stress related genes and inhibits the immunoregulatory function of NK cells publication-title: Oncotarget doi: 10.18632/oncotarget.12616 contributor: fullname: Schneider – volume: 8 start-page: 636 year: 2002 ident: ref_18 article-title: A view to a kill: Signals triggering cytotoxicity publication-title: Clin. Cancer Res. contributor: fullname: Djeu – volume: 66 start-page: i5 year: 2010 ident: ref_36 article-title: Risk assessment and prognostic factors for mould-related diseases in immunocompromised patients publication-title: J. Antimicrob. Chemother. doi: 10.1093/jac/dkq437 contributor: fullname: Pagano – volume: 114 start-page: 1640 year: 2009 ident: ref_8 article-title: Human Natural Killer Cells Are Able to Kill Aspergillus Fumigatus but Not Via the Perforin - Granzyme Pathway publication-title: Blood doi: 10.1182/blood.V114.22.1640.1640 contributor: fullname: Bouzani – volume: 7 start-page: 6138 year: 2017 ident: ref_7 article-title: CD56 Is a Pathogen Recognition Receptor on Human Natural Killer Cells publication-title: Sci. Rep. doi: 10.1038/s41598-017-06238-4 contributor: fullname: Ziegler – volume: 203 start-page: 430 year: 2011 ident: ref_9 article-title: Human Natural Killer Cells Exhibit Direct Activity Against Aspergillus fumigatus Hyphae, But Not Against Resting Conidia publication-title: J. Infect. Dis. doi: 10.1093/infdis/jiq062 contributor: fullname: Schmidt – volume: 7 start-page: e01823-15 year: 2016 ident: ref_34 article-title: Aspergillus Cell Wall Chitin Induces Anti- and Proinflammatory Cytokines in Human PBMCs via the Fc-γ Receptor/Syk/PI3K Pathway publication-title: mBio doi: 10.1128/mBio.01823-15 contributor: fullname: Becker – volume: 198 start-page: 176 year: 2008 ident: ref_31 article-title: Caspofungin modulates inflammatory responses to Aspergillus fumigatus through stage-specific effects on fungal β-glucan exposure publication-title: J. Infect. Dis. doi: 10.1086/589304 contributor: fullname: Hohl – volume: 65 start-page: 453 year: 2012 ident: ref_1 article-title: Clinical epidemiology of 960 patients with invasive aspergillosis from the PATH Alliance registry publication-title: J. Infect. doi: 10.1016/j.jinf.2012.08.003 contributor: fullname: Steinbach – volume: 6 start-page: 1322 year: 2015 ident: ref_3 article-title: Optimizing Outcomes in Immunocompromised Hosts: Understanding the Role of Immunotherapy in Invasive Fungal Diseases publication-title: Front. Microbiol. doi: 10.3389/fmicb.2015.01322 contributor: fullname: Ravikumar – volume: 187 start-page: 1369 year: 2011 ident: ref_4 article-title: Human NK Cells Display Important Antifungal Activity againstAspergillus fumigatus, Which Is Directly Mediated by IFN-γ Release publication-title: J. Immunol. doi: 10.4049/jimmunol.1003593 contributor: fullname: Bouzani – volume: 29 start-page: 89 year: 2009 ident: ref_12 article-title: Expansion and Activation of Natural Killer Cells for Cancer Immunotherapy publication-title: Ann. Lab. Med. doi: 10.3343/kjlm.2009.29.2.89 contributor: fullname: Cho – volume: 13 start-page: 151 year: 2011 ident: ref_33 article-title: Aspergillus fumigatus cell wall components differentially modulate host TLR2 and TLR4 responses publication-title: Microbes Infect. doi: 10.1016/j.micinf.2010.10.005 contributor: fullname: Chai – volume: 16 start-page: 3901 year: 2010 ident: ref_37 article-title: Cytotoxicity of Activated Natural Killer Cells against Pediatric Solid Tumors publication-title: Clin. Cancer Res. doi: 10.1158/1078-0432.CCR-10-0735 contributor: fullname: Cho – volume: 182 start-page: 4306 year: 2009 ident: ref_23 article-title: Early NK Cell-Derived IFN-γ Is Essential to Host Defense in Neutropenic Invasive Aspergillosis publication-title: J. Immunol. doi: 10.4049/jimmunol.0803462 contributor: fullname: Park – volume: 4 start-page: 574 year: 2016 ident: ref_13 article-title: Expanded and Activated Natural Killer Cells for Immunotherapy of Hepatocellular Carcinoma publication-title: Cancer Immunol. Res. doi: 10.1158/2326-6066.CIR-15-0229 contributor: fullname: Kamiya – volume: 3 start-page: e04177 year: 2014 ident: ref_30 article-title: Recognition of tumor cells by Dectin-1 orchestrates innate immune cells for anti-tumor responses publication-title: eLife doi: 10.7554/eLife.04177 contributor: fullname: Chiba – volume: 162 start-page: 1633 year: 1999 ident: ref_16 article-title: Role of TNF-α in pulmonary host defense in murine invasive aspergillosis publication-title: J. Immunol. doi: 10.4049/jimmunol.162.3.1633 contributor: fullname: Mehrad – volume: 220 start-page: 714 year: 2015 ident: ref_32 article-title: Chitin enhances serum IgE in Aspergillus fumigatus induced allergy in mice publication-title: Immunobiol. doi: 10.1016/j.imbio.2015.01.002 contributor: fullname: Dubey – volume: 77 start-page: 2184 year: 2009 ident: ref_14 article-title: Modulation of Toll-Like Receptor 2 (TLR2) and TLR4 Responses by Aspergillus fumigatus publication-title: Infect. Immun. doi: 10.1128/IAI.01455-08 contributor: fullname: Chai – volume: 1 start-page: 109 year: 2014 ident: ref_17 article-title: Perforin: An important player in immune response publication-title: Central Eur. J. Immunol. doi: 10.5114/ceji.2014.42135 contributor: fullname: Popko – volume: 20 start-page: 452 year: 2013 ident: ref_5 article-title: Natural Killer Cells and Antifungal Host Response publication-title: Clin. Vaccine Immunol. doi: 10.1128/CVI.00606-12 contributor: fullname: Schmidt – volume: 65 start-page: 477 year: 2016 ident: ref_11 article-title: Selection and expansion of natural killer cells for NK cell-based immunotherapy publication-title: Cancer Immunol. Immunother. doi: 10.1007/s00262-016-1792-y contributor: fullname: Becker – volume: 97 start-page: 1348 year: 2012 ident: ref_22 article-title: Highly activated and expanded natural killer cells for multiple myeloma immunotherapy publication-title: Haematologica doi: 10.3324/haematol.2011.056747 contributor: fullname: Garg – volume: 56 start-page: 403 year: 2013 ident: ref_2 article-title: Minireview: Host defence in invasive aspergillosis publication-title: Mycoses doi: 10.1111/myc.12052 contributor: fullname: Roilides – volume: 7 start-page: 692 year: 2017 ident: ref_24 article-title: Granule-Dependent Natural Killer Cell Cytotoxicity to Fungal Pathogens publication-title: Front. Immunol. doi: 10.3389/fimmu.2016.00692 contributor: fullname: Ogbomo – volume: 6 start-page: 33 year: 2005 ident: ref_28 article-title: Dectin-1: A signalling non-TLR pattern-recognition receptor publication-title: Nat. Rev. Immunol. doi: 10.1038/nri1745 contributor: fullname: Brown – ident: ref_35 doi: 10.1371/journal.pone.0013418 – volume: 6 start-page: 15 year: 2004 ident: ref_19 article-title: Ex vivo expansion of natural killer cells for clinical applications publication-title: Cytotherapy doi: 10.1080/14653240310004548 contributor: fullname: Klingemann – volume: 54 start-page: 169 year: 2015 ident: ref_6 article-title: Human Invariant Natural Killer T cells possess immune-modulating functions duringAspergillusinfection publication-title: Med Mycol. contributor: fullname: Bouzani – volume: 74 start-page: 318 year: 1996 ident: ref_25 article-title: Exacerbation of invasive aspergillosis by the immunosuppressive fungal metabolite, gliotoxin publication-title: Immunol. Cell Biol. doi: 10.1038/icb.1996.57 contributor: fullname: Sutton – volume: 69 start-page: 4010 year: 2009 ident: ref_20 article-title: Expansion of Highly Cytotoxic Human Natural Killer Cells for Cancer Cell Therapy publication-title: Cancer Res. doi: 10.1158/0008-5472.CAN-08-3712 contributor: fullname: Fujisaki – volume: 347 start-page: 408 year: 2002 ident: ref_27 article-title: Voriconazole versus Amphotericin B for Primary Therapy of Invasive Aspergillosis publication-title: New Engl. J. Med. doi: 10.1056/NEJMoa020191 contributor: fullname: Herbrecht |
| SSID | ssj0001586993 |
| Score | 2.2375247 |
| Snippet | Invasive aspergillosis (IA) is a major opportunistic fungal infection in patients with haematological malignancies. Morbidity and mortality rates are high... |
| SourceID | doaj pubmedcentral proquest crossref |
| SourceType | Open Website Open Access Repository Aggregation Database |
| StartPage | 231 |
| SubjectTerms | antifungal immunity Aspergillus expanded natural killer cells fungal infection immune evasion immune recognition |
| SummonAdditionalLinks | – databaseName: Directory of Open Access Journals dbid: DOA link: http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwrV07T8MwELZQxcCCeIrykhGsURPHsZOxrVq1IDq1UrfITyiqEkQKgn_P2WmhmVhYE0uxv7vkvsudPyN0Rzi8RjYygSSUBTTWNMjCWAShlNraVEeRP7XkccJGM3o_T-ZbR325nrBaHrgGrsO1lglxrqdCCrFOhnGiKCE6o5mOuPVf35BsJVP1_uCUQeSt9UhjyOs7L6Vl4LAkjhoRyAv1N9hlszdyK9gMD9D-miXibj27Q7RjiiO02yuByX0do7Gv8-PB56v7A6zxRHjxDPzg9_XhvlkuKywqPK0VAzDwUjwuPoTrVMddJw3-BCPLalGdoNlwMO2PgvWRCAGsOVoFMrLCKC0FU9Ip0ymZwZoyYGmMUQYAh8ba2MQkS6ViEshQrKgOrbY8Uxbo3ilqFWVhzhBODOCqEqqogaRKcqGddJ9lXAkdMqHa6HYDU_5aK1_kkDE4MPNfMNuo5xD8GeHUqv0FsGG-tmH-lw3b6GaDfw7e7UoWojDle5X7unBKU0rbiDcM03hi806xePY62Zw7aRly_h9TvEB7xGXarpeFX6LW6u3dXAEdWclr73nfGx7euA priority: 102 providerName: Directory of Open Access Journals |
| Title | Using Expanded Natural Killer Cells as Therapy for Invasive Aspergillosis |
| URI | https://search.proquest.com/docview/2452984844 https://pubmed.ncbi.nlm.nih.gov/PMC7712362 https://doaj.org/article/7ddb520318c04175b035c422d949d17f |
| Volume | 6 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3fT9swED4BmyZeEINNK7DK03gNzQ_HTh6brhVsokIIJN4i_4ROJalIQfDfc3baQV73FClx5Ph8yX1f7vwZ4Djm-BrZyAQypiygiaZBHiYiCKXU1mY6ivyuJedTdnpNf9-kNxuQrtfC-KJ9JWcn1fz-pJrd-drKxb0arOvEBhfnI86dZkg82IRNDL_vKHq7NDhjGHRbKdIEKf3gb20Z-ioimW34hPw9w7DHOnHIy_V3MGa3QvJdyJnsws4KK5Jh-0yfYcNUe_CxqBHPvezDmc_2k_Hzwv0H1mQqvIQG-eNX95GRmc8bIhpy1eoGEESn5Kx6Eq5enQydQPgttqybWfMFrifjq9FpsNoYIVA0jpaBjKwwSkvBlHT6dErmOLwcsRpjlKGZQ2NtYpI4z6RiEiFRoqgOrbY8VxZB31fYqurKfAOSGpnGKqWKGqRWkgvtBPws40rokAnVg59rM5WLVv-iRN7g7Fq-2bUHhbPgvxZOs9qfqB9uy9XMlVxr7Mt9RFRIEbXIMElxPLHOaa4jbnvwY23_En3cJS5EZerHpvTZ4YxmlPaAdyam02P3CjqPV8teOcvBf995CNuxI9mujIUfwdby4dF8RySylH34MCx-FRM8FuPpxWXfM_q-98dXBljkRw |
| link.rule.ids | 230,314,727,780,784,864,885,2102,27924,27925,33745,53791,53793 |
| linkProvider | National Library of Medicine |
| linkToHtml | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT-MwEB7xWLFcEOxDWxZYo91raB6OnRzbCtQutNpDkbhFfkJXJalIQfDvd-y0C7lyTRw5Hk8y32fPfAb4FXP8jGxkAhlTFtBE0yAPExGEUmprMx1F_tSS8YQNr-nvm_RmA9J1LYxP2ldydlbO78_K2Z3PrVzcq-46T6z7Zzzg3GmGxN1N2E4TnkdvSHpTHJwxDLuNGGmCpL77t7IMvRWxzC7sIIPPMPCxViTygv0tlNnOkXwTdC72YW-FFkmveasD2DDlJ_jQrxDRvXyGkd_vJ-fPC7cSrMlEeBENcunr-8jAzOc1ETWZNsoBBPEpGZVPwmWsk56TCL_FllU9q7_A9cX5dDAMVkcjBIrG0TKQkRVGaSmYkk6hTskch5cjWmOMMjR0aKxNTBLnmVRMIihKFNWh1ZbnyiLs-wpbZVWab0BSI9NYpVRRg-RKcqGdhJ9lXAkdMqE68HNtpmLRKGAUyBycXYtXu3ag7yz4v4VTrfYXqofbYjV3Bdca-3K_ERVSxC0yTFIcT6xzmuuI2w6cru1foJe7rQtRmuqxLvz-cEYzSjvAWxPT6rF9B93H62Wv3OXw3U_-gI_D6fiquBpNLr_Dbuwot0tq4UewtXx4NMeIS5byxHvhP4dT45s |
| linkToPdf | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1LT9wwEB61tEJcKgqtuuVlVK4hL8dOjrCwYgusOIDELfJz2WpJVmSp6L9n7OzSzZVr4sjxeJL5Ps_4M8BRwvEzsrEJZEJZQFNNgyJKRRBJqa3NdRz7U0uuR-zijv6-z-5XjvryRftKTo6r6eNxNXnwtZWzRxUu68TCm-s-504zJAln2oYf4VOWopOtEPV2g3DOMPS2gqQpEvvwT20ZeizimQ1YRxafY_BjnWjkRfs7SLNbJ7kSeAab8GWBGMlJ-2Zf4YOptuDzaY2o7t82DH3On5y_zNxqsCYj4YU0yKXf40f6ZjptiGjIbaseQBCjkmH1V7iqdXLiZMLH2LJuJs03uBuc3_YvgsXxCIGiSTwPZGyFUVoKpqRTqVOywOEViNgYowyNHRlrU5MmRS4VkwiMUkV1ZLXlhbII_b7DWlVX5geQzMgsURlV1CDBklxoJ-NnGVdCR0yoHvxamqmctSoYJbIHZ9fyv117cOos-NbCKVf7C_XTuFzMX8m1xr7cr0RFFLGLjNIMx5PoghY65rYHh0v7l-jpLn0hKlM_N6XPEec0p7QHvDMxnR67d9CFvGb2wmV-vvvJA1i_ORuUV8PR5Q5sJI51u7oWvgtr86dns4fQZC73vRO-As2E5K4 |
| 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=Using+Expanded+Natural+Killer+Cells+as+Therapy+for+Invasive+Aspergillosis&rft.jtitle=Journal+of+fungi+%28Basel%29&rft.au=Win+Mar+Soe&rft.au=Joan+Hui+Juan+Lim&rft.au=David+L.+Williams&rft.au=Jessamine+Geraldine+Goh&rft.date=2020-10-17&rft.pub=MDPI+AG&rft.eissn=2309-608X&rft.volume=6&rft.issue=4&rft.spage=231&rft_id=info:doi/10.3390%2Fjof6040231&rft.externalDBID=DOA&rft.externalDocID=oai_doaj_org_article_7ddb520318c04175b035c422d949d17f |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=2309-608X&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=2309-608X&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=2309-608X&client=summon |