Department of Life Sciences, State University of Bahia, Salvador, Brazil.
Institute of Health Sciences, Federal University of Bahia, Salvador, Brazil.
Front Immunol. 2021 Feb 22;12:622051. doi: 10.3389/fimmu.2021.622051. eCollection 2021.
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.
遗传和表观遗传因素被认为是宿主-寄生虫相互作用的关键。关于这些因素在人类感染 中的作用,数据有限。在这里,我们描述了遗传因素作为巴西儿童对 产生 Th2 免疫反应的决定因素的潜在作用。从儿童中收集粪便样本以通过显微镜检测 ,并在全血培养物中培养外周血白细胞 (PBL) 以检测细胞因子 (IL-5、IL-10 和 IL-13) 。测量血浆中的抗 IgE 和 IgG4 水平。从 PBL 中提取 DNA 并使用 Illumina 2.5 人类 Omni Beadchip 进行基因分型。鉴定与 反应相关的候选基因,并鉴定这些选定基因中与对 的 Th2 免疫反应相关的 SNV。进行单体型、基因表达和表观遗传分析以鉴定与 Th2 免疫反应相关的潜在关联。对来自 1189 名儿童的样本进行的 GWAS 鉴定 为候选基因,IL-21R 被选为进一步分析的生物学相关连锁基因。 和 中的变体与 Th2 免疫反应的标志物相关:与未感染个体相比,感染个体的 PBL 中特异性 IgE 和 IL-5/IL-13 增加。在感染儿童中, 而不是 基因表达被抑制,并且在 启动子区域观察到增加的甲基化。这是第一项表明在儿童 感染期间 和 中的遗传变异与 Th2 免疫反应之间存在关联的研究。/途径可能为治疗 Th2 介导的疾病提供潜在目标。