WSB1 and IL21R Genetic Variants Are Involved in Th2 Immune Responses to Ascaris lumbricoides

• Published in: Frontiers in immunology Vol. 12; p. 622051
• Main Authors: Carneiro, Valdirene Leão, da Silva, Hugo Bernardino Ferreira, Queiroz, Gerson de Almeida, Veiga, Rafael Valente, Oliveira, Pablo Rafael Silveira, Carneiro, Norma Vilany Queiroz, Pires, Anaque de Oliveira, da Silva, Raimon Rios, Sena, Flavia, Belitardo, Emilia, Nascimento, Regina, Silva, Milca, Marques, Cintia Rodrigues, Costa, Ryan Dos Santos, Alcantra-Neves, Neuza Maria, Barreto, Mauricio L, Cooper, Philip J, Figueiredo, Camila Alexandrina
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 22-02-2021
• Subjects: Ascaris lumbricoides; IL21R; immunity; Immunology; polymorphism; WSB1; IL21R; Ascaris lumbricoides; polymorphism; WSB1; immunity
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.622051

Genetic and epigenetic factors are considered to be critical for host-parasite interactions. There are limited data on the role of such factors during human infections with
. Here, we describe the potential role of genetic factors as determinants of the Th2 immune response to
in Brazilian children. Stool samples were collected from the children to detect
by microscopy and peripheral blood leukocytes (PBLs) were cultured in whole blood cultures for detection of cytokines (IL-5, IL-10, and IL-13)
. Levels of anti-
IgE and IgG4 were measured in plasma. DNA was extracted from PBLs and genotyped using Illumina 2.5 Human Omni Beadchip. Candidate genes associated with
responses were identified and SNVs in these selected genes associated with the Th2 immune response to
. Haplotype, gene expression, and epigenetic analyses were done to identify potential associations with Th2 immune responses. GWAS on samples from 1,189 children identified
as a candidate gene, and IL-21R was selected as a biologically relevant linked gene for further analysis. Variants in
and
were associated with markers of Th2 immune responses: increased
-specific IgE and IL-5/IL-13 by PBLs from infected compared to uninfected individuals. In infected children,
but not
gene expression was suppressed and increased methylation was observed in the
promoter region. This is the first study to show an association between genetic variants in
and
and Th2 immune responses during
infections in children.
/
pathways could provide a potential target for the treatment of Th2-mediated diseases.