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 2017-02, Vol.11 (2), p.e0005413-e0005413
• Main Authors: Dos Santos, Jéssica Cristina, Heinhuis, Bas, Gomes, Rodrigo Saar, Damen, Michelle S M A, Real, Fernando, Mortara, Renato A, Keating, Samuel T, Dinarello, Charles A, Joosten, Leo A B, Ribeiro-Dias, Fátima
• Format: Article
• Language: English
• Subjects: Antimicrobial Cationic Peptides - metabolism; beta-Defensins - metabolism; Biology and Life Sciences; Care and treatment; Cell Line; Cytokines; Cytokines - metabolism; Development and progression; Funding; Gene Expression; Gene Knockdown Techniques; Genetic aspects; Health aspects; Humans; Infections; Infectious diseases; Interleukins; Interleukins - metabolism; Internal medicine; Leishmania braziliensis - immunology; Leishmania mexicana - immunology; Leishmaniasis; Life Sciences; Macrophages - immunology; Macrophages - parasitology; Medical research; Medicine; Medicine and Health Sciences; Nitric oxide; Nitric Oxide - metabolism; Parasites; Parasitic diseases; Research and Analysis Methods; Studies; Tropical diseases; Tumor necrosis factor-TNF; Vector-borne diseases; Viral infections
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0005413

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.