Genetic variation in Interleukin-32 influence the immune response against New World Leishmania species and susceptibility to American Tegumentary Leishmaniasis.
PLoS Negl Trop Dis
; 14(2): e0008029, 2020 02.
Article
in En
| MEDLINE
| ID: mdl-32023240
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genetic Variation
/
Interleukins
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Leishmaniasis, Cutaneous
/
Genetic Predisposition to Disease
/
Leishmania
Limits:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
Country/Region as subject:
America do sul
/
Brasil
Language:
En
Journal:
PLoS Negl Trop Dis
Journal subject:
MEDICINA TROPICAL
Year:
2020
Document type:
Article
Affiliation country: