Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Zhong, Wujuan
    • Affiliation: Gillings School of Global Public Health, Department of Biostatistics
  • Kollipara, Avinash
    • Affiliation: School of Medicine, Department of Pediatrics
  • Liu, Yutong
    • Affiliation: Gillings School of Global Public Health, Department of Biostatistics
  • Wang, Yuhan
    • Affiliation: Gillings School of Global Public Health, Department of Biostatistics
  • O'Connell, Catherine M.
    • Affiliation: School of Medicine, Department of Pediatrics
  • Poston, Taylor B.
    • Affiliation: School of Medicine, Department of Pediatrics
  • Yount, Kacy
    • Affiliation: School of Medicine, Department of Pediatrics
  • Wiesenfeld, Harold C.
    • Other Affiliation: The University of Pittsburgh School of Medicine
  • Hillier, Sharon L.
    • Other Affiliation: The University of Pittsburgh School of Medicine
  • Li, Yun
    • Affiliation: Gillings School of Global Public Health, Department of Biostatistics
  • Darville, Toni
    • Affiliation: School of Medicine, Department of Pediatrics
  • Zheng, Xiaojing
    • Affiliation: Gillings School of Global Public Health, Department of Biostatistics
Abstract
  • Objectives Identify genetic loci of enhanced susceptibility to Chlamydial trachomatis (Ct) upper genital tract infection in women.MethodsWe performed an integrated analysis of DNA genotypes and blood-derived mRNA profiles from 200 Ct-exposed women to identify expression quantitative trait loci (eQTL) and determine their association with endometrial chlamydial infection using a mediation test. We further evaluated the effect of a lead eQTL on the expression of CD151 by immune cells from women with genotypes associated with low and high whole blood expression of CD151, respectively. Results We identified cis-eQTLs modulating mRNA expression of 81 genes (eGenes) associated with altered risk of ascending infection. In women with endometrial infection, eGenes involved in proinflammatory signaling were upregulated. Downregulated eGenes included genes involved in T cell functions pivotal for chlamydial control. eGenes encoding molecules linked to metabolism of tryptophan, an essential chlamydial nutrient, and formation of epithelial tight junctions were also downregulated in women with endometrial infection. A lead eSNP rs10902226 was identified regulating CD151, a tetrospanin molecule important for immune cell adhesion and migration and T cell proliferation. Further in vitro experiments showed that women with a CC genotype at rs10902226 had reduced rates of endometrial infection with increased CD151 expression in whole blood and T cells when compared to women with a GG genotype. Conclusions We discovered genetic variants associated with altered risk for Ct ascension. A lead eSNP for CD151 is a candidate genetic marker for enhanced CD4 T cell function and reduced susceptibility.
Date of publication
Keyword
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
License
  • Attribution 4.0 International
Journal title
  • Frontiers in Immunology
Journal volume
  • 13
Language
  • English
Version
  • Publisher
ISSN
  • 1664-3224

Relations

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details fimmu-13-1001255.pdf 2022-10-07 Public Download