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

PLoS Negl Trop Dis 2020 02 5;14(2):e0008029. Epub 2020 Feb 5.

Radboud Institute for Molecular Sciences (RILMS), Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0008029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7028298PMC
February 2020

Publication Analysis

Top Keywords

tegumentary leishmaniasis
8
american tegumentary
8
il32 rs4786370
8
adaptive cytokine
4
influencing innate
4
expression influencing
4
cytokine production
4
innate adaptive
4
leishmania exposure
4
leishmaniasis patients
4
patients control
4
107 american
4
cohort 107
4
exposure brazilian
4
brazilian cohort
4
production leishmania
4
modulating il-32γ
4
antigens time
4
time functional
4
braziliensis antigens
4

Similar Publications