1. Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis.
- Author
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Dos Santos JC, Leite Quixabeira VB, Teodoro Silva MV, Damen MSMA, Schraa K, Jaeger M, Oosting M, Keating ST, Dorta ML, Alves Pinto S, Bugalho Duarte F, de Araújo Pereira LI, Netea MG, Ribeiro-Dias F, and Joosten LAB
- Subjects
- Adult, Aged, Brazil epidemiology, Cytokines genetics, Cytokines metabolism, Female, Gene Expression Regulation immunology, Humans, Lectins, C-Type genetics, Lectins, C-Type metabolism, Leishmaniasis, Cutaneous epidemiology, Leishmaniasis, Cutaneous immunology, Leishmaniasis, Cutaneous metabolism, Male, Middle Aged, Nod2 Signaling Adaptor Protein genetics, Nod2 Signaling Adaptor Protein metabolism, Protein Isoforms, Toll-Like Receptor 4 genetics, Toll-Like Receptor 4 metabolism, Genetic Predisposition to Disease, Genetic Variation, Interleukins genetics, Leishmania classification, Leishmaniasis, Cutaneous genetics
- Abstract
Interleukin-32 is a novel inflammatory mediator that has been described to be important in the immunopathogenesis and control of infections caused by Leishmania parasites. By performing experiments with primary human cells in vitro, we demonstrate that the expression of IL-32 isoforms is dependent on the time exposed to L. amazonensis and L. braziliensis antigens. Moreover, for the first time we show the functional consequences of three different genetic variations in the IL32 (rs4786370, rs4349147, rs1555001) modulating IL-32γ expression, influencing innate and adaptive cytokine production after Leishmania exposure. Using a Brazilian cohort of 107 American Tegumentary Leishmaniasis patients and a control cohort of 245 healthy individuals, the IL32 rs4786370 genetic variant was associated with protection against ATL, whereas the IL32 rs4349147 was associated with susceptibility to the development of localized cutaneous and mucosal leishmaniasis. These novel insights may help improve therapeutic strategies and lead to benefits for patients suffering from Leishmania infections., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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