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PLoS Negl Trop Dis. 2020 Feb 5;14(2):e0008029. doi: 10.1371/journal.pntd.0008029. [Epub ahead of print]

Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis.

Author information

1
Radboud Institute for Molecular Sciences (RILMS), Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
2
Laboratório de Imunidade Natural (LIN), Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
3
Instituto Goiano de Oncologia e Hematologia (INGOH), Goiânia, Goiás, Brazil.
4
Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati Ohio, United States of America.
5
Faculdade de Medicina, Universidade Federal de Goiás, Goiânia, Goiás, Brazil.
6
Hospital Unique, Goiânia, Goiás, Brazil.
7
Hospital de Doenças Tropicais Anuar Auad, Goiânia-Goiás, Brazil.
8
Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Germany.

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.

PMID:
32023240
DOI:
10.1371/journal.pntd.0008029
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Conflict of interest statement

The authors have declared that no competing interests exist.

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