Paracoccidioidomycosis (PCM) is a systemic
fungal disease caused by Paracoccidioides spp., whose clinical outcome depends on immune response.
Interleukin 32 (IL-32) is a
cytokine present in inflammatory and
infectious diseases, including bacterial, virus and
protozoan infections. Its role in
fungal disease remains unclear. The axis
IL-15, IL-32 and
vitamin D leads to microbicidal capacity against intracellular pathogens. Thus, the aims of this study were to investigate the production of IL-32 during Paracoccidioides spp.
infection and whether this
cytokine and
IL-15 can increase P. brasiliensis control in a
vitamin D dependent manner. IL-32 was highly detected in oral lesions from patients with PCM. In addition, high production of this
cytokine was intracellularly detected in peripheral blood mononuclear cells (PBMCs) from healthy donors after exposure to particulated P. brasiliensis
antigens (PbAg). The IL-32γ
isoform was predominantly expressed, but there was
mRNA alternative splicing for IL-32α
isoform. The induction of IL-32 was dependent on
Dectin-1 receptor.
Infection of PBMCs with P. brasiliensis yeasts did not significantly induce IL-32 production even after activation with exogenous IFN-γ or
IL-15 treatments. Although
IL-15 was a potent inducer of IL-32 production, treatment with this
cytokine did not increase the fungal control unless
vitamin D was present in high levels. In this case, both
IL-15 and IL-32 increased fungicidal activity of PBMCs. Together, data showed that IL-32 is present in lesions of PCM, PbAg induces IL-32, and the axis of IL-15/IL-32/
vitamin D can contribute to control
fungal infection. The data suggest that exposure to molecules from P. brasiliensis, as β-
glucans, is needed to induce IL-32 production since only heat-killed and sonicated P. brasiliensis yeasts were able to increase IL-32, which was blocked by anti-Dectin-1
antibodies. This is the first description about IL-15/IL-32/
vitamin D pathway role in P. brasiliensis
infection.