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

• Main Authors: Jéssica Cristina Dos Santos (Author), Bas Heinhuis (Author), Rodrigo Saar Gomes (Author), Michelle S M A Damen (Author), Fernando Real (Author), Renato A Mortara (Author), Samuel T Keating (Author), Charles A Dinarello (Author), Leo A B Joosten (Author), Fátima Ribeiro-Dias (Author)
• Format: Book
• Published: Public Library of Science (PLoS), 2017-02-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1935-2727
1935-2735
10.1371/journal.pntd.0005413