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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Published in |
PLoS Neglected Tropical Diseases, February 2017
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DOI | 10.1371/journal.pntd.0005413 |
Pubmed ID | |
Authors |
Jéssica Cristina dos Santos, Bas Heinhuis, Rodrigo Saar Gomes, Michelle S. M. A. Damen, Fernando Real, Renato A. Mortara, Samuel T. Keating, Charles A. Dinarello, Leo A. B. Joosten, Fátima Ribeiro-Dias |
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. |
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