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

• Autor(a) principal: dos Santos, Jessica Cristina
• Data de Publicação: 2017
• Outros Autores: Heinhuis, Bas, Gomes, Rodrigo Saar, Damen, Michelle S. M. A., Real, Fernando [UNIFESP], Mortara, Renato A. [UNIFESP], Keating, Samuel T., Dinarello, Charles A., Joosten, Leo A. B., Ribeiro-Dias, Fatima
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• dARK ID: ark:/48912/001300000k4t2
• Texto Completo: http://dx.doi.org/10.1371/journal.pntd.0005413; https://repositorio.unifesp.br/handle/11600/55193

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.