PMID- 33771629 OWN - NLM STAT- MEDLINE DCOM- 20210617 LR - 20210617 IS - 1096-1208 (Electronic) IS - 0882-4010 (Linking) VI - 154 DP - 2021 May TI - Paracoccidioidesbrasiliensis induces IL-32 and is controlled by IL-15/IL-32/vitamin D pathway in vitro. PG - 104864 LID - S0882-4010(21)00136-4 [pii] LID - 10.1016/j.micpath.2021.104864 [doi] AB - 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-32gamma isoform was predominantly expressed, but there was mRNA alternative splicing for IL-32alpha 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-gamma 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 beta-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. CI - Copyright (c) 2021 Elsevier Ltd. All rights reserved. FAU - Guimaraes de Matos, Grazzielle AU - Guimaraes de Matos G AD - Laboratorio de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saude Publica, Universidade Federal de Goias, Goiania, Goias, Brazil. FAU - Barroso de Figueiredo, Ana Marina AU - Barroso de Figueiredo AM AD - Laboratorio de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saude Publica, Universidade Federal de Goias, Goiania, Goias, Brazil. FAU - Diniz Goncalves, Pedro Hugo AU - Diniz Goncalves PH AD - Laboratorio de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saude Publica, Universidade Federal de Goias, Goiania, Goias, Brazil. FAU - Luiz de Lima Silva, Lucas AU - Luiz de Lima Silva L AD - Laboratorio de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saude Publica, Universidade Federal de Goias, Goiania, Goias, Brazil. FAU - Bastista, Aline Carvalho AU - Bastista AC AD - Faculdade de Odontologia, Universidade Federal de Goias, Goiania, Goias, Brazil. FAU - Borges, Clayton Luiz AU - Borges CL AD - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade Federal de Goias (UFG), Goiania, Goias, Brazil. FAU - Maria de Almeida Soares, Celia AU - Maria de Almeida Soares C AD - Laboratorio de Biologia Molecular, Instituto de Ciencias Biologicas, Universidade Federal de Goias (UFG), Goiania, Goias, Brazil. FAU - Joosten, Leo A B AU - Joosten LAB AD - Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, the Netherlands. FAU - Ribeiro-Dias, Fatima AU - Ribeiro-Dias F AD - Laboratorio de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saude Publica, Universidade Federal de Goias, Goiania, Goias, Brazil. Electronic address: fdias@ufg.br. LA - eng PT - Journal Article DEP - 20210323 PL - England TA - Microb Pathog JT - Microbial pathogenesis JID - 8606191 RN - 0 (Interleukin-15) RN - 0 (Interleukins) RN - 1406-16-2 (Vitamin D) SB - IM MH - Humans MH - Interleukin-15 MH - Interleukins MH - Leukocytes, Mononuclear MH - *Paracoccidioides MH - *Paracoccidioidomycosis MH - Vitamin D OTO - NOTNLM OT - Interleukin-15 OT - Interleukin-32 OT - Paracoccidioides brasiliensis OT - Vitamin D OT - human mononuclear cells EDAT- 2021/03/28 06:00 MHDA- 2021/06/22 06:00 CRDT- 2021/03/27 05:49 PHST- 2020/11/29 00:00 [received] PHST- 2021/02/19 00:00 [revised] PHST- 2021/03/05 00:00 [accepted] PHST- 2021/03/28 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2021/03/27 05:49 [entrez] AID - S0882-4010(21)00136-4 [pii] AID - 10.1016/j.micpath.2021.104864 [doi] PST - ppublish SO - Microb Pathog. 2021 May;154:104864. doi: 10.1016/j.micpath.2021.104864. Epub 2021 Mar 23.