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

• Published in: PLOS Neglected Tropical Diseases
• Main 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
• Format: Article in Journal/Newspaper
• Language: English
• Published: Public Library of Science (PLoS) 2017
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Public aspects of medicine; RA1-1270; Arctic
• Online Access: https://doi.org/10.1371/journal.pntd.0005413; https://doaj.org/article/16254dd2fbcc4966b9d3480570e35e4a

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.