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Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species

BACKGROUND: Interleukin-32 (IL-32) is expressed in lesions of patients with American Tegumentary Leishmaniasis (ATL), but its precise role in the disease remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, silencing and overexpression of IL-32 was performed in THP-1-derived macrop...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344527/
https://www.ncbi.nlm.nih.gov/pubmed/28241012
http://dx.doi.org/10.1371/journal.pntd.0005413
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author 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
author_facet 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
author_sort dos Santos, Jéssica Cristina
collection PubMed
description BACKGROUND: Interleukin-32 (IL-32) is expressed in lesions of patients with American Tegumentary Leishmaniasis (ATL), but its precise role in the disease remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: Thus, endogenous IL-32 is a crucial cytokine involved in the host defense against Leishmania parasites.
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spelling pubmed-53445272017-03-29 Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species 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 PLoS Negl Trop Dis Research Article BACKGROUND: Interleukin-32 (IL-32) is expressed in lesions of patients with American Tegumentary Leishmaniasis (ATL), but its precise role in the disease remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: Thus, endogenous IL-32 is a crucial cytokine involved in the host defense against Leishmania parasites. Public Library of Science 2017-02-27 /pmc/articles/PMC5344527/ /pubmed/28241012 http://dx.doi.org/10.1371/journal.pntd.0005413 Text en © 2017 dos Santos et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
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
Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species
title Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species
title_full Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species
title_fullStr Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species
title_full_unstemmed Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species
title_short Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species
title_sort cytokines and microbicidal molecules regulated by il-32 in thp-1-derived human macrophages infected with new world leishmania species
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344527/
https://www.ncbi.nlm.nih.gov/pubmed/28241012
http://dx.doi.org/10.1371/journal.pntd.0005413
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