Carneiro, VL;
da Silva, HBF;
Queiroz, GDA;
Veiga, RV;
Oliveira, PRS;
Carneiro, NVQ;
Pires, ADO;
da Silva, RR;
Sena, F;
Belitardo, E;
et al.
Carneiro, VL; da Silva, HBF; Queiroz, GDA; Veiga, RV; Oliveira, PRS; Carneiro, NVQ; Pires, ADO; da Silva, RR; Sena, F; Belitardo, E; Nascimento, R; Silva, M; Marques, CR; Costa, RDS; Alcantra-Neves, NM; Barreto, ML; Cooper, PJ; Figueiredo, CA
(2021)
WSB1 and IL21R Genetic Variants Are Involved in Th2 Immune Responses to Ascaris lumbricoides.
Front Immunol, 12.
p. 622051.
ISSN 1664-3224
https://doi.org/10.3389/fimmu.2021.622051
SGUL Authors: Cooper, Philip John
Abstract
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 Ascaris lumbricoides. Here, we describe the potential role of genetic factors as determinants of the Th2 immune response to A. lumbricoides in Brazilian children. Stool samples were collected from the children to detect A. lumbricoides by microscopy and peripheral blood leukocytes (PBLs) were cultured in whole blood cultures for detection of cytokines (IL-5, IL-10, and IL-13) in vitro. Levels of anti-A. lumbricoides 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 A. lumbricoides responses were identified and SNVs in these selected genes associated with the Th2 immune response to A. lumbricoides. Haplotype, gene expression, and epigenetic analyses were done to identify potential associations with Th2 immune responses. GWAS on samples from 1,189 children identified WSB1 as a candidate gene, and IL-21R was selected as a biologically relevant linked gene for further analysis. Variants in WSB1 and IL21R were associated with markers of Th2 immune responses: increased A. lumbricoides-specific IgE and IL-5/IL-13 by PBLs from infected compared to uninfected individuals. In infected children, WSB1 but not IL21R gene expression was suppressed and increased methylation was observed in the WSB1 promoter region. This is the first study to show an association between genetic variants in WSB1 and IL21R and Th2 immune responses during A. lumbricoides infections in children. WSB1/IL21R pathways could provide a potential target for the treatment of Th2-mediated diseases.
Item Type: |
Article
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Additional Information: |
Copyright © 2021 Carneiro, da Silva, Queiroz, Veiga, Oliveira, Carneiro, Pires, da Silva, Sena, Belitardo, Nascimento, Silva, Marques, Costa, Alcantra-Neves, Barreto, Cooper and Figueiredo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
Keywords: |
Ascaris lumbricoides, IL21R, WSB1, immunity, polymorphism |
SGUL Research Institute / Research Centre: |
Academic Structure > Infection and Immunity Research Institute (INII) |
Journal or Publication Title: |
Front Immunol |
ISSN: |
1664-3224 |
Language: |
eng |
Dates: |
Date | Event |
---|
22 February 2021 | Published | 29 January 2021 | Accepted |
|
Publisher License: |
Creative Commons: Attribution 4.0 |
Projects: |
|
PubMed ID: |
33692795 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/113064 |
Publisher's version: |
https://doi.org/10.3389/fimmu.2021.622051 |
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