Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity
ObjectivesIdentify 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)...
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| Format: | Article |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1001255/full |
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| author | Wujuan Zhong Avinash Kollipara Yutong Liu Yuhan Wang Catherine M. O’Connell Taylor B. Poston Kacy Yount Harold C. Wiesenfeld Sharon L. Hillier Yun Li Yun Li Toni Darville Xiaojing Zheng Xiaojing Zheng |
| author_facet | Wujuan Zhong Avinash Kollipara Yutong Liu Yuhan Wang Catherine M. O’Connell Taylor B. Poston Kacy Yount Harold C. Wiesenfeld Sharon L. Hillier Yun Li Yun Li Toni Darville Xiaojing Zheng Xiaojing Zheng |
| author_sort | Wujuan Zhong |
| collection | DOAJ |
| description | ObjectivesIdentify 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.ResultsWe 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.ConclusionsWe 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. |
| first_indexed | 2024-04-11T09:08:19Z |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T09:08:19Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-6c8270e983b4469a8c83442361dd69842022-12-22T04:32:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.10012551001255Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrityWujuan Zhong0Avinash Kollipara1Yutong Liu2Yuhan Wang3Catherine M. O’Connell4Taylor B. Poston5Kacy Yount6Harold C. Wiesenfeld7Sharon L. Hillier8Yun Li9Yun Li10Toni Darville11Xiaojing Zheng12Xiaojing Zheng13Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesThe University of Pittsburgh School of Medicine and the Magee-Womens Research Institute, Pittsburgh, PA, United StatesThe University of Pittsburgh School of Medicine and the Magee-Womens Research Institute, Pittsburgh, PA, United StatesDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesDepartment of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United StatesObjectivesIdentify 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.ResultsWe 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.ConclusionsWe 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.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1001255/fullChlamydial trachomatisupper genital tract infection in womengenetic marker for host susceptibilitycis-eQTLsblood T cells and T cell subsetsCD151 |
| spellingShingle | Wujuan Zhong Avinash Kollipara Yutong Liu Yuhan Wang Catherine M. O’Connell Taylor B. Poston Kacy Yount Harold C. Wiesenfeld Sharon L. Hillier Yun Li Yun Li Toni Darville Xiaojing Zheng Xiaojing Zheng Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity Frontiers in Immunology Chlamydial trachomatis upper genital tract infection in women genetic marker for host susceptibility cis-eQTLs blood T cells and T cell subsets CD151 |
| title | Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity |
| title_full | Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity |
| title_fullStr | Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity |
| title_full_unstemmed | Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity |
| title_short | Genetic susceptibility loci for Chlamydia trachomatis endometrial infection influence expression of genes involved in T cell function, tryptophan metabolism and epithelial integrity |
| title_sort | genetic susceptibility loci for chlamydia trachomatis endometrial infection influence expression of genes involved in t cell function tryptophan metabolism and epithelial integrity |
| topic | Chlamydial trachomatis upper genital tract infection in women genetic marker for host susceptibility cis-eQTLs blood T cells and T cell subsets CD151 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1001255/full |
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