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

PLoS Negl Trop Dis. 2017 Feb 27;11(2):e0005413. doi: 10.1371/journal.pntd.0005413. eCollection 2017 Feb.

Abstract

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.

MeSH terms

  • Antimicrobial Cationic Peptides / metabolism
  • Cathelicidins
  • Cell Line
  • Cytokines / metabolism*
  • Gene Expression
  • Gene Knockdown Techniques
  • Humans
  • Interleukins / metabolism*
  • Leishmania braziliensis / immunology*
  • Leishmania mexicana / immunology*
  • Macrophages / immunology*
  • Macrophages / parasitology*
  • Nitric Oxide / metabolism
  • beta-Defensins / metabolism

Substances

  • Antimicrobial Cationic Peptides
  • Cytokines
  • DEFB4A protein, human
  • IL32 protein, human
  • Interleukins
  • beta-Defensins
  • Nitric Oxide
  • Cathelicidins

Grants and funding

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and CAPES (project 401887/2013-8 Fátima Ribeiro-Dias, coordinator; Leonardus A.B. Joosten, PVE fellow of CNPq). FR-D and RAM are fellow researchers of CNPq, JCS is PhD student, fellow of CNPq; RSG and FR are post doctors, fellows of CNPq. BH is supported by a grant from the Dutch Arthritis Foundation (13-3-302). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.