The immune modulatory peptide FhHDM-1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages
The NLRP3 inflammasome is a multimeric protein complex that controls the production of IL-1β, a cytokine that influences the development of both innate and adaptive immune responses. Helminth parasites secrete molecules that interact with innate immune cells, modulating their activity to ultimately...
Saved in:
Published in | The FASEB journal Vol. 31; no. 1; p. 85 |
---|---|
Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.01.2017
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
Abstract | The NLRP3 inflammasome is a multimeric protein complex that controls the production of IL-1β, a cytokine that influences the development of both innate and adaptive immune responses. Helminth parasites secrete molecules that interact with innate immune cells, modulating their activity to ultimately determine the phenotype of differentiated T cells, thus creating an immune environment that is conducive to sustaining chronic infection. We show that one of these molecules, FhHDM-1, a cathelicidin-like peptide secreted by the helminth parasite, Fasciola hepatica, inhibits the activation of the NLRP3 inflammasome resulting in reduced secretion of IL-1β by macrophages. FhHDM-1 had no effect on the synthesis of pro-IL-1β. Rather, the inhibitory effect was associated with the capacity of the peptide to prevent acidification of the endolysosome. The activation of cathepsin B protease by lysosomal destabilization was prevented in FhHDM-1-treated macrophages. By contrast, peptide derivatives of FhHDM-1 that did not alter the lysosomal pH did not inhibit secretion of IL-1β. We propose a novel immune modulatory strategy used by F. hepatica, whereby secretion of the FhHDM-1 peptide impairs the activation of NLRP3 by lysosomal cathepsin B protease, which prevents the downstream production of IL-1β and the development of protective T helper 1 type immune responses that are detrimental to parasite survival.-Alvarado, R., To, J., Lund, M. E., Pinar, A., Mansell, A., Robinson, M. W., O'Brien, B. A., Dalton, J. P., Donnelly, S. The immune modulatory peptide FhHDM-1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages. |
---|---|
AbstractList | The NLRP3 inflammasome is a multimeric protein complex that controls the production of IL-1β, a cytokine that influences the development of both innate and adaptive immune responses. Helminth parasites secrete molecules that interact with innate immune cells, modulating their activity to ultimately determine the phenotype of differentiated T cells, thus creating an immune environment that is conducive to sustaining chronic infection. We show that one of these molecules, FhHDM-1, a cathelicidin-like peptide secreted by the helminth parasite, Fasciola hepatica, inhibits the activation of the NLRP3 inflammasome resulting in reduced secretion of IL-1β by macrophages. FhHDM-1 had no effect on the synthesis of pro-IL-1β. Rather, the inhibitory effect was associated with the capacity of the peptide to prevent acidification of the endolysosome. The activation of cathepsin B protease by lysosomal destabilization was prevented in FhHDM-1-treated macrophages. By contrast, peptide derivatives of FhHDM-1 that did not alter the lysosomal pH did not inhibit secretion of IL-1β. We propose a novel immune modulatory strategy used by F. hepatica, whereby secretion of the FhHDM-1 peptide impairs the activation of NLRP3 by lysosomal cathepsin B protease, which prevents the downstream production of IL-1β and the development of protective T helper 1 type immune responses that are detrimental to parasite survival.-Alvarado, R., To, J., Lund, M. E., Pinar, A., Mansell, A., Robinson, M. W., O'Brien, B. A., Dalton, J. P., Donnelly, S. The immune modulatory peptide FhHDM-1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages. |
Author | Alvarado, Raquel Dalton, John P Donnelly, Sheila Pinar, Anita Lund, Maria E Mansell, Ashley O'Brien, Bronwyn A To, Joyce Robinson, Mark W |
Author_xml | – sequence: 1 givenname: Raquel surname: Alvarado fullname: Alvarado, Raquel organization: School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia – sequence: 2 givenname: Joyce surname: To fullname: To, Joyce organization: School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia – sequence: 3 givenname: Maria E surname: Lund fullname: Lund, Maria E organization: School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia – sequence: 4 givenname: Anita surname: Pinar fullname: Pinar, Anita organization: Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia; and – sequence: 5 givenname: Ashley surname: Mansell fullname: Mansell, Ashley organization: Monash Institute of Medical Research, Monash University, Clayton, Victoria, Australia; and – sequence: 6 givenname: Mark W surname: Robinson fullname: Robinson, Mark W organization: School of Biological Sciences, Queen's University, Belfast, Northern Ireland – sequence: 7 givenname: Bronwyn A surname: O'Brien fullname: O'Brien, Bronwyn A organization: School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia – sequence: 8 givenname: John P surname: Dalton fullname: Dalton, John P organization: School of Biological Sciences, Queen's University, Belfast, Northern Ireland – sequence: 9 givenname: Sheila surname: Donnelly fullname: Donnelly, Sheila email: sheila.donnelly@uts.edu.au organization: School of Life Sciences, University of Technology Sydney, Sydney, New South Wales, Australia; sheila.donnelly@uts.edu.au |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27682204$$D View this record in MEDLINE/PubMed |
BookMark | eNo1kMlOwzAYhC0EogscuSK_QIqXOE2OqFCKVBZV5Vw59p_GVWxHsVspb8UjErbTSKNvvsNM0LnzDhC6oWRGSZHdVYcZI1QQQgrenaExFZwkWZ6REZqEcBh6Smh2iUZsnuWMkXSMPrc1YGPt0QG2Xh8bGX3X4xbaaDTgZb16eEkoDqA6iKBx2eM4LGporHGxxksZlPGNHJpWRqMkbjs4gYsBv6437xwbVzXSWhm8BSxVNKcB8-5bZFxtShON22Nw2jd98AMlmwEz2lSD7Ic0DlupOt_Wcg_hCl1Usglw_ZdT9LF83C5Wyfrt6Xlxv06UoGKTsJTMU6I1FBRYxoTIqjnlgnNaFUXFRFYqTSFNVUrzQnCtylRyMWe8KvM8LzWbottfb3ssLehd2xkru373fx37AnY0c-U |
CitedBy_id | crossref_primary_10_1096_fj_201901480RR crossref_primary_10_1007_s00109_021_02122_x crossref_primary_10_1021_acsinfecdis_9b00157 crossref_primary_10_3389_fcimb_2021_667272 crossref_primary_10_1038_s41598_021_86125_1 crossref_primary_10_1016_j_ebiom_2018_08_054 crossref_primary_10_1111_imcb_12297 crossref_primary_10_1016_j_jaci_2018_01_050 crossref_primary_10_3389_fimmu_2019_00552 crossref_primary_10_1155_2023_5544819 crossref_primary_10_3390_microorganisms12020371 crossref_primary_10_1186_s13071_018_3250_5 crossref_primary_10_1016_j_jaci_2017_09_005 crossref_primary_10_1017_S0031182022000749 crossref_primary_10_1016_j_intimp_2021_107756 crossref_primary_10_1111_pim_12410 crossref_primary_10_1186_s13071_020_3882_0 crossref_primary_10_3389_fimmu_2017_00883 crossref_primary_10_1111_imcb_12171 crossref_primary_10_1042_BSR20231918 crossref_primary_10_1111_imm_13231 crossref_primary_10_3390_ph14121209 crossref_primary_10_1371_journal_pone_0188520 crossref_primary_10_3389_fendo_2023_1205219 crossref_primary_10_1016_j_actatropica_2020_105548 crossref_primary_10_3389_fmicb_2018_00843 crossref_primary_10_1371_journal_pntd_0008470 crossref_primary_10_1007_s12026_024_09496_3 crossref_primary_10_1186_s12864_020_07326_y crossref_primary_10_1016_j_actatropica_2022_106578 crossref_primary_10_1371_journal_pntd_0010854 crossref_primary_10_1111_pim_12916 crossref_primary_10_1016_j_mib_2018_09_002 crossref_primary_10_1007_s00436_019_06405_8 crossref_primary_10_3389_fimmu_2020_02182 crossref_primary_10_1111_all_13944 crossref_primary_10_1080_21505594_2021_1996520 crossref_primary_10_3389_fimmu_2018_00664 crossref_primary_10_1016_j_ijbiomac_2023_124649 crossref_primary_10_1007_s13105_018_0644_y crossref_primary_10_1111_pim_12982 crossref_primary_10_1371_journal_pntd_0005963 crossref_primary_10_3389_fimmu_2023_1018076 crossref_primary_10_1016_j_immuni_2018_10_016 crossref_primary_10_1016_j_pt_2019_10_012 crossref_primary_10_3389_fvets_2022_832062 crossref_primary_10_3389_fimmu_2017_00453 |
ContentType | Journal Article |
Copyright | FASEB. |
Copyright_xml | – notice: FASEB. |
DBID | CGR CUY CVF ECM EIF NPM |
DOI | 10.1096/fj.201500093r |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
Discipline | Biology |
EISSN | 1530-6860 |
ExternalDocumentID | 27682204 |
Genre | Research Support, Non-U.S. Gov't Journal Article |
GrantInformation_xml | – fundername: Biotechnology and Biological Sciences Research Council grantid: BB/L019612/1 |
GroupedDBID | --- -DZ -~X .55 0R~ 0VX 123 18M 1OB 1OC 29H 2WC 33P 34G 39C 3O- 4.4 53G 5GY 5RE 85S AAHHS AANLZ ABCUV ABDNZ ABEFU ABJNI ABOCM ACCFJ ACCZN ACGFS ACIWK ACNCT ACPOU ACPRK ACXQS ACYGS ADKYN ADZMN AEEZP AEIGN AENEX AEQDE AEUYR AFFNX AFFPM AFRAH AGCDD AHBTC AI. AITYG AIURR AIWBW AIZAD AJBDE ALMA_UNASSIGNED_HOLDINGS ALUQN AMYDB BFHJK BIYOS C1A CGR CS3 CUY CVF DCZOG DU5 D~5 E3Z EBS ECM EIF EJD F20 F5P F9R FRP H13 HGLYW HZ~ H~9 J5H L7B LATKE LEEKS MEWTI MVM NEJ NPM O9- OHT OVD Q-A RHF RHI RJQFR ROL SAMSI SJN SUPJJ TEORI TFA TR2 TWZ VH1 W8F WH7 WHG WOQ WXSBR X7M XJT XOL XSW Y6R YBU YCJ YHG YKV YNH YSK Z0Y ZCA ZE2 ZGI ZXP ~KM |
ID | FETCH-LOGICAL-c515R-240740dde91e262556f7135331f99f256bcd1e44c418953dcb4a35723fb888bd2 |
IngestDate | Sat Sep 28 08:50:45 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 1 |
Keywords | liver fluke IL-1β trematode lysosome |
Language | English |
License | FASEB. |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c515R-240740dde91e262556f7135331f99f256bcd1e44c418953dcb4a35723fb888bd2 |
OpenAccessLink | https://doi.org/10.1096/fj.201500093r |
PMID | 27682204 |
ParticipantIDs | pubmed_primary_27682204 |
PublicationCentury | 2000 |
PublicationDate | January 2017 |
PublicationDateYYYYMMDD | 2017-01-01 |
PublicationDate_xml | – month: 01 year: 2017 text: January 2017 |
PublicationDecade | 2010 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | The FASEB journal |
PublicationTitleAlternate | FASEB J |
PublicationYear | 2017 |
SSID | ssj0001016 |
Score | 2.4777784 |
Snippet | The NLRP3 inflammasome is a multimeric protein complex that controls the production of IL-1β, a cytokine that influences the development of both innate and... |
SourceID | pubmed |
SourceType | Index Database |
StartPage | 85 |
SubjectTerms | Animals Cathepsin B - genetics Cathepsin B - metabolism Cytokines - genetics Cytokines - metabolism Fasciola hepatica - genetics Fasciola hepatica - metabolism Gene Expression Regulation - physiology Helminth Proteins - genetics Helminth Proteins - metabolism Hydrogen-Ion Concentration Lysosomes - metabolism Macrophages - drug effects Macrophages - physiology Mice Mice, Inbred BALB C NLR Family, Pyrin Domain-Containing 3 Protein - genetics NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Silicon Dioxide - toxicity |
Title | The immune modulatory peptide FhHDM-1 secreted by the helminth Fasciola hepatica prevents NLRP3 inflammasome activation by inhibiting endolysosomal acidification in macrophages |
URI | https://www.ncbi.nlm.nih.gov/pubmed/27682204 |
Volume | 31 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lj9MwELa6ICQuiPcbzYFbFWhiN0mPC2xVoaValV1pbys7cZSsmqTaZFcqv4ofwQ9jJrZJujwEXKLKdiy389WeGc_Mx9hrxSX-0VTgpWESelSvxFORnHpcplmk_SibZF20xTJcnIiPp9PT0ejbIGrpslVvki-_zCv5H6liG8qVsmT_QbI_JsUG_IzyxSdKGJ9_LeOCEjw0MdoQERfdmG8oUCXV43m--PDJ88cNaYat1TTxjVyvy6Jq8_FcNpStIrGF4qoTSRUDrrqUt-Xh6ohTpBYCppRNXZqqG8Z_SxMVVV6ooouZ1lVar7dNjaOo8EBSpBR-JF0UZSmJJSzHfasZasK09vn-54N34-FXJeitr-SFTDsX7krisdXHgJhbonrbo_Hw0rIio8kv-6yKI8oyNvGaRSuHng0_Gng2tNuN0baNDeGA267toTGEpdl7DfXPT0cC2mgkx3MK4-vYH_jFcBxKdFN2-AjQ8goCQ4b8595rFbpd1x7bi2KiD1mSx8hqA-QdsbVdcSVvd9ZBlajtu9esmk67Ob7L7lizBPYNxu6xka7us1uGqHT7gH1FaYFBGvRIA4s0sEgDhzRQW0CkgUMaOKSBQxo4pEGHNBgiDXqk0UQ90mAHabCDNBwGA6Q9ZCfzg-P3C89yfXgJatQruuSLxATP2pmvg5Dq4mVEHsm5n81mGerlKkl9LUQi_Hg25WmihOTTKOCZiuNYpcEjdqOqK_2EgUCjQ_MoCHkiRKYD5XONB5dE2x2Nk0n4lD02P_XZxhR0OXNCePbbnufsdo_QF-xmhjuIfonqaKtedfL-DvH9kO8 |
link.rule.ids | 780 |
linkProvider | National Library of Medicine |
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=The+immune+modulatory+peptide+FhHDM-1+secreted+by+the+helminth+Fasciola+hepatica+prevents+NLRP3+inflammasome+activation+by+inhibiting+endolysosomal+acidification+in+macrophages&rft.jtitle=The+FASEB+journal&rft.au=Alvarado%2C+Raquel&rft.au=To%2C+Joyce&rft.au=Lund%2C+Maria+E&rft.au=Pinar%2C+Anita&rft.date=2017-01-01&rft.eissn=1530-6860&rft.volume=31&rft.issue=1&rft.spage=85&rft_id=info:doi/10.1096%2Ffj.201500093r&rft_id=info%3Apmid%2F27682204&rft_id=info%3Apmid%2F27682204&rft.externalDocID=27682204 |