Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis.
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 o...
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doaj-4b4f16bfe8924b5c958c7729a0749dd72021-03-03T07:54:38ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352020-02-01142e000802910.1371/journal.pntd.0008029Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis.Jéssica Cristina Dos SantosValéria Bernadete Leite QuixabeiraMuriel Vilela Teodoro SilvaMichelle S M A DamenKiki SchraaMartin JaegerMarije OostingSamuel T KeatingMiriam Leandro DortaSebastião Alves PintoFernanda Bugalho DuarteLedice Inácia de Araújo PereiraMihai G NeteaFátima Ribeiro-DiasLeo A B JoostenInterleukin-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.https://doi.org/10.1371/journal.pntd.0008029 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jéssica Cristina Dos Santos Valéria Bernadete Leite Quixabeira Muriel Vilela Teodoro Silva Michelle S M A Damen Kiki Schraa Martin Jaeger Marije Oosting Samuel T Keating Miriam Leandro Dorta Sebastião Alves Pinto Fernanda Bugalho Duarte Ledice Inácia de Araújo Pereira Mihai G Netea Fátima Ribeiro-Dias Leo A B Joosten |
spellingShingle |
Jéssica Cristina Dos Santos Valéria Bernadete Leite Quixabeira Muriel Vilela Teodoro Silva Michelle S M A Damen Kiki Schraa Martin Jaeger Marije Oosting Samuel T Keating Miriam Leandro Dorta Sebastião Alves Pinto Fernanda Bugalho Duarte Ledice Inácia de Araújo Pereira Mihai G Netea Fátima Ribeiro-Dias Leo A B Joosten Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis. PLoS Neglected Tropical Diseases |
author_facet |
Jéssica Cristina Dos Santos Valéria Bernadete Leite Quixabeira Muriel Vilela Teodoro Silva Michelle S M A Damen Kiki Schraa Martin Jaeger Marije Oosting Samuel T Keating Miriam Leandro Dorta Sebastião Alves Pinto Fernanda Bugalho Duarte Ledice Inácia de Araújo Pereira Mihai G Netea Fátima Ribeiro-Dias Leo A B Joosten |
author_sort |
Jéssica Cristina Dos Santos |
title |
Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis. |
title_short |
Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis. |
title_full |
Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis. |
title_fullStr |
Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis. |
title_full_unstemmed |
Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis. |
title_sort |
genetic variation in interleukin-32 influence the immune response against new world leishmania species and susceptibility to american tegumentary leishmaniasis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Neglected Tropical Diseases |
issn |
1935-2727 1935-2735 |
publishDate |
2020-02-01 |
description |
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. |
url |
https://doi.org/10.1371/journal.pntd.0008029 |
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