%0 Journal Article
%T Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis
%A Fernanda Bugalho Duarte
%A F¨¢tima Ribeiro-Dias
%A J¨¦ssica Cristina dos Santos
%A Kiki Schraa
%A Ledice In¨¢cia de Ara¨²jo Pereira
%A Leo A. B. Joosten
%A Marije Oosting
%A Martin Jaeger
%A Michelle S. M. A. Damen
%A Mihai G. Netea
%A Miriam Leandro Dorta
%A Muriel Vilela Teodoro Silva
%A Samuel T. Keating
%A Sebasti£¿o Alves Pinto
%A Val¨¦ria Bernadete Leite Quixabeira
%J -
%D 2020
%R 10.1371/journal.pntd.0008029
%X 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-32¦Ã 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
%K Leishmania
%K Cytokines
%K Lesions
%K Genetic polymorphism
%K Human genetics
%K Gene expression
%K Leishmaniasis
%K Brazil
%U https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0008029