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

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2017
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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-32 gamma, and show that intracellular IL-32. protein production is dependent on endogenous TNF alpha. Silencing or overexpression of IL-32 demonstrated that this cytokine is closely related to TNF alpha 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 beta-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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Plos Neglected Tropical Diseases. San Francisco, v. 11, n. 2, p. -, 2017.
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