Paracoccidioidesbrasiliensis induces IL-32 and is controlled by IL-15/IL-32/vitamin D pathway in vitro

• Published in: Microbial pathogenesis 2021-05, Vol.154, p.104864-104864, Article 104864
• Main Authors: Guimarães de Matos, Grazzielle, Barroso de Figueiredo, Ana Marina, Diniz Gonçalves, Pedro Hugo, Luiz de Lima Silva, Lucas, Bastista, Aline Carvalho, Borges, Clayton Luiz, Maria de Almeida Soares, Célia, Joosten, Leo A.B., Ribeiro-Dias, Fátima
• Format: Article
• Language: English
• Subjects: human mononuclear cells; Interleukin-15; Interleukin-32; Paracoccidioides brasiliensis; Vitamin D
• ISSN: 0882-4010; 1096-1208
• DOI: 10.1016/j.micpath.2021.104864

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. [Display omitted] •IL-32 is present in human lesions caused by Paracoccidioides spp.•P. brasiliensis particulated antigens induce IL-32 production, especially IL-32γ.•Induction of IL-32 by P. brasiliensis is partially dependent on Dectin-1 receptor.•IL-15/IL-32/vitamin D axis promotes the killing of P. brasiliensis by human cells.