A Critical Overview of Interleukin 32 in Leishmaniases

Abstract

Interleukin-32 (IL-32) has several immune regulatory properties, which have driven its investigation in the context of various diseases. IL-32 expression is reported to be induced in the lesions of patients with American tegumentary leishmaniasis (ATL) by the New World Leishmania spp. that are responsible for causing ATL and visceral leishmaniasis (VL). IL-32 expression may elevate the inflammatory process through the induction of pro-inflammatory cytokines and also via mechanisms directed to kill the parasites. The genetic variants of IL-32 might be associated with the resistance or susceptibility to ATL, while different isoforms of IL-32 could be associated with distinct T helper lymphocyte profiles. IL-32 also determines the transcriptional profile in the bone marrow progenitor cells to mediate the trained immunity induced by β-glucan and BCG, thereby contributing to the resistance against Leishmania. IL-32γ is essential for the vitamin D-dependent microbicidal pathway for parasite control. In this context, the present review report briefly discusses the data retrieved from the studies conducted on IL-32 in leishmaniasis in humans and mice to highlight the current challenges to understanding the role of IL-32 in leishmaniasis.

Keywords: IL-32; Leishmania; genetic; tegumentary leishmaniasis; trained immunity; visceral leishmaniasis; vitamin D.

Figure 1

Interleukin-32 in Leishmania infections. (A) Human macrophages derived from the monocyte cell line THP-1 were infected with L. amazonensis (La) or L. braziliensis (Lb) (MOI 5:1) after IL-32γ silencing (siRNA) or overexpression (plasmid) for evaluation of cytokine and antimicrobial molecules. (B, C) PBMCs from healthy individuals genotyped for three IL32 variants were exposed to La (B) or Lb (C) promastigote lysates for cytokine evaluation (innate - TNF-α, IL-1β, IL-6/24 h; acquired immunity: IL-22, IL-17, IFN-γ/seven days) and association with ATL and its clinical outcome; expression of cytokines and different IL-32 isoforms were evaluated in lesions of ATL patients and positive correlations were obtained. (D) Human monocyte-derived macrophages were infected with Lb after priming with recombinant cytokines - IL-15 (inducer of IL-32) and/or IL-32γ to evaluate vitamin D-dependent microbicidal pathway and NO and ROS production.