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Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species
Interleukin-32 (IL-32) is expressed in lesions of patients with American Tegumentary Leishmaniasis (ATL), but its precise role in the disease remains unknown. In the present study, silencing and overexpression of IL-32 was performed in THP-1-derived macrophages infected with Leishmania (Viannia) bra...
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Published in: | PLoS neglected tropical diseases 2017-02, Vol.11 (2), p.e0005413-e0005413 |
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creator | Dos Santos, Jéssica Cristina Heinhuis, Bas Gomes, Rodrigo Saar Damen, Michelle S M A Real, Fernando Mortara, Renato A Keating, Samuel T Dinarello, Charles A Joosten, Leo A B Ribeiro-Dias, Fátima |
description | Interleukin-32 (IL-32) is expressed in lesions of patients with American Tegumentary Leishmaniasis (ATL), but its precise role in the disease remains unknown.
In the present study, silencing and overexpression of IL-32 was performed in THP-1-derived macrophages infected with Leishmania (Viannia) braziliensis or L. (Leishmania) amazonensis to investigate the role of IL-32 in infection. We report that Leishmania species induces IL-32γ, and show that intracellular IL-32γ protein production is dependent on endogenous TNFα. Silencing or overexpression of IL-32 demonstrated that this cytokine is closely related to TNFα and IL-8. Remarkably, the infection index was augmented in the absence of IL-32 and decreased in cells overexpressing this cytokine. Mechanistically, these effects can be explained by nitric oxide cathelicidin and β-defensin 2 production regulated by IL-32.
Thus, endogenous IL-32 is a crucial cytokine involved in the host defense against Leishmania parasites. |
doi_str_mv | 10.1371/journal.pntd.0005413 |
format | article |
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In the present study, silencing and overexpression of IL-32 was performed in THP-1-derived macrophages infected with Leishmania (Viannia) braziliensis or L. (Leishmania) amazonensis to investigate the role of IL-32 in infection. We report that Leishmania species induces IL-32γ, and show that intracellular IL-32γ protein production is dependent on endogenous TNFα. Silencing or overexpression of IL-32 demonstrated that this cytokine is closely related to TNFα and IL-8. Remarkably, the infection index was augmented in the absence of IL-32 and decreased in cells overexpressing this cytokine. Mechanistically, these effects can be explained by nitric oxide cathelicidin and β-defensin 2 production regulated by IL-32.
Thus, endogenous IL-32 is a crucial cytokine involved in the host defense against Leishmania parasites.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0005413</identifier><identifier>PMID: 28241012</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Antimicrobial Cationic Peptides - metabolism ; beta-Defensins - metabolism ; Biology and Life Sciences ; Care and treatment ; Cell Line ; Cytokines ; Cytokines - metabolism ; Development and progression ; Funding ; Gene Expression ; Gene Knockdown Techniques ; Genetic aspects ; Health aspects ; Humans ; Infections ; Infectious diseases ; Interleukins ; Interleukins - metabolism ; Internal medicine ; Leishmania braziliensis - immunology ; Leishmania mexicana - immunology ; Leishmaniasis ; Life Sciences ; Macrophages - immunology ; Macrophages - parasitology ; Medical research ; Medicine ; Medicine and Health Sciences ; Nitric oxide ; Nitric Oxide - metabolism ; Parasites ; Parasitic diseases ; Research and Analysis Methods ; Studies ; Tropical diseases ; Tumor necrosis factor-TNF ; Vector-borne diseases ; Viral infections</subject><ispartof>PLoS neglected tropical diseases, 2017-02, Vol.11 (2), p.e0005413-e0005413</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Public Library of Science. 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: species. PLoS Negl Trop Dis 11(2): e0005413. doi:10.1371/journal.pntd.0005413</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>2017 dos Santos et al 2017 dos Santos et al</rights><rights>2017 Public Library of Science. 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: species. PLoS Negl Trop Dis 11(2): e0005413. doi:10.1371/journal.pntd.0005413</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c658t-66ff62e915af2a14262ae091576db19aa3d62c872de119b7111c32c51fcca3d93</citedby><cites>FETCH-LOGICAL-c658t-66ff62e915af2a14262ae091576db19aa3d62c872de119b7111c32c51fcca3d93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/1878076103/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/1878076103?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25752,27923,27924,37011,37012,44589,53790,53792,74897</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28241012$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03796751$$DView record in HAL$$Hfree_for_read</backlink></links><search><contributor>Santiago, Helton da Costa</contributor><creatorcontrib>Dos Santos, Jéssica Cristina</creatorcontrib><creatorcontrib>Heinhuis, Bas</creatorcontrib><creatorcontrib>Gomes, Rodrigo Saar</creatorcontrib><creatorcontrib>Damen, Michelle S M A</creatorcontrib><creatorcontrib>Real, Fernando</creatorcontrib><creatorcontrib>Mortara, Renato A</creatorcontrib><creatorcontrib>Keating, Samuel T</creatorcontrib><creatorcontrib>Dinarello, Charles A</creatorcontrib><creatorcontrib>Joosten, Leo A B</creatorcontrib><creatorcontrib>Ribeiro-Dias, Fátima</creatorcontrib><title>Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>Interleukin-32 (IL-32) is expressed in lesions of patients with American Tegumentary Leishmaniasis (ATL), but its precise role in the disease remains unknown.
In the present study, silencing and overexpression of IL-32 was performed in THP-1-derived macrophages infected with Leishmania (Viannia) braziliensis or L. (Leishmania) amazonensis to investigate the role of IL-32 in infection. We report that Leishmania species induces IL-32γ, and show that intracellular IL-32γ protein production is dependent on endogenous TNFα. Silencing or overexpression of IL-32 demonstrated that this cytokine is closely related to TNFα and IL-8. Remarkably, the infection index was augmented in the absence of IL-32 and decreased in cells overexpressing this cytokine. Mechanistically, these effects can be explained by nitric oxide cathelicidin and β-defensin 2 production regulated by IL-32.
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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PLoS neglected tropical diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dos Santos, Jéssica Cristina</au><au>Heinhuis, Bas</au><au>Gomes, Rodrigo Saar</au><au>Damen, Michelle S M A</au><au>Real, Fernando</au><au>Mortara, Renato A</au><au>Keating, Samuel T</au><au>Dinarello, Charles A</au><au>Joosten, Leo A B</au><au>Ribeiro-Dias, Fátima</au><au>Santiago, Helton da Costa</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2017-02-27</date><risdate>2017</risdate><volume>11</volume><issue>2</issue><spage>e0005413</spage><epage>e0005413</epage><pages>e0005413-e0005413</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><abstract>Interleukin-32 (IL-32) is expressed in lesions of patients with American Tegumentary Leishmaniasis (ATL), but its precise role in the disease remains unknown.
In the present study, silencing and overexpression of IL-32 was performed in THP-1-derived macrophages infected with Leishmania (Viannia) braziliensis or L. (Leishmania) amazonensis to investigate the role of IL-32 in infection. We report that Leishmania species induces IL-32γ, and show that intracellular IL-32γ protein production is dependent on endogenous TNFα. Silencing or overexpression of IL-32 demonstrated that this cytokine is closely related to TNFα and IL-8. Remarkably, the infection index was augmented in the absence of IL-32 and decreased in cells overexpressing this cytokine. Mechanistically, these effects can be explained by nitric oxide cathelicidin and β-defensin 2 production regulated by IL-32.
Thus, endogenous IL-32 is a crucial cytokine involved in the host defense against Leishmania parasites.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28241012</pmid><doi>10.1371/journal.pntd.0005413</doi><oa>free_for_read</oa></addata></record> |
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subjects | Antimicrobial Cationic Peptides - metabolism beta-Defensins - metabolism Biology and Life Sciences Care and treatment Cell Line Cytokines Cytokines - metabolism Development and progression Funding Gene Expression Gene Knockdown Techniques Genetic aspects Health aspects Humans Infections Infectious diseases Interleukins Interleukins - metabolism Internal medicine Leishmania braziliensis - immunology Leishmania mexicana - immunology Leishmaniasis Life Sciences Macrophages - immunology Macrophages - parasitology Medical research Medicine Medicine and Health Sciences Nitric oxide Nitric Oxide - metabolism Parasites Parasitic diseases Research and Analysis Methods Studies Tropical diseases Tumor necrosis factor-TNF Vector-borne diseases Viral infections |
title | Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species |
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