Anna Gibbs1, Katie Healy2, Vilde Kaldhusdal1, Christopher Sundling1, Mathias Franzén-Boger1, Gabriella Edfeldt1, Marcus Buggert3, Julie Lajoie4,5, Keith R Fowke4,5,6,7, Joshua Kimani4,5,6, Douglas S Kwon8, Sonia Andersson9, Johan K Sandberg3, Kristina Broliden1, Haleh Davanian2, Margaret Sällberg Chen2, Annelie Tjernlund1. 1. Department of Medicine Solna, Division of Infectious Diseases, Karolinska Institutet, Department of Infectious Diseases, Karolinska University Hospital, Center for Molecular Medicine, Stockholm, Sweden. 2. Department of Dental Medicine, Division of Oral Diagnostics and Surgery, Karolinska Institutet, Stockholm, Sweden. 3. Department of Medicine Huddinge, Center for Infectious Medicine, Karolinska Institutet, Stockholm, Sweden. 4. Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Canada. 5. Department of Medical Microbiology, University of Nairobi, Nairobi, Kenya. 6. Partners for Health and Development in Africa, Nairobi, Kenya. 7. Department of Community Health Sciences, University of Manitoba, Winnipeg, Canada. 8. Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Cambridge, Massachusetts, USA. 9. Department of Women's and Children's Health, Division of Obstetrics and Gynecology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
Abstract
BACKGROUND: Mucosa-associated invariant T (MAIT) cells are innate-like T cells with specialized antimicrobial functions. Circulating MAIT cells are depleted in chronic human immunodeficiency virus (HIV) infection, but studies examining this effect in peripheral tissues, such as the female genital tract, are lacking. METHODS: Flow cytometry was used to investigate circulating MAIT cells in a cohort of HIV-seropositive (HIV+) and HIV-seronegative (HIV-) female sex workers (FSWs), and HIV- lower-risk women (LRW). In situ staining and quantitative polymerase chain reaction were performed to explore the phenotype of MAIT cells residing in paired cervicovaginal tissue. The cervicovaginal microbiome was assessed by means of 16S ribosomal RNA gene sequencing. RESULTS: MAIT cells in the HIV+ FSW group were low in frequency in the circulation but preserved in the ectocervix. MAIT cell T-cell receptor gene segment usage differed between the HIV+ and HIV- FSW groups. The TRAV1-2-TRAJ20 transcript was the most highly expressed MAIT TRAJ gene detected in the ectocervix in the HIV+ FSW group. MAIT TRAVJ usage was not associated with specific genera in the vaginal microbiome. CONCLUSIONS: MAIT cells residing in the ectocervix are numerically preserved irrespective of HIV infection status and displayed dominant expression of TRAV1-2-TRAJ20. These findings have implications for understanding the role of cervical MAIT cells in health and disease.
BACKGROUND: Mucosa-associated invariant T (MAIT) cells are innate-like T cells with specialized antimicrobial functions. Circulating MAIT cells are depleted in chronic human immunodeficiency virus (HIV) infection, but studies examining this effect in peripheral tissues, such as the female genital tract, are lacking. METHODS: Flow cytometry was used to investigate circulating MAIT cells in a cohort of HIV-seropositive (HIV+) and HIV-seronegative (HIV-) female sex workers (FSWs), and HIV- lower-risk women (LRW). In situ staining and quantitative polymerase chain reaction were performed to explore the phenotype of MAIT cells residing in paired cervicovaginal tissue. The cervicovaginal microbiome was assessed by means of 16S ribosomal RNA gene sequencing. RESULTS: MAIT cells in the HIV+ FSW group were low in frequency in the circulation but preserved in the ectocervix. MAIT cell T-cell receptor gene segment usage differed between the HIV+ and HIV- FSW groups. The TRAV1-2-TRAJ20 transcript was the most highly expressed MAIT TRAJ gene detected in the ectocervix in the HIV+ FSW group. MAIT TRAVJ usage was not associated with specific genera in the vaginal microbiome. CONCLUSIONS: MAIT cells residing in the ectocervix are numerically preserved irrespective of HIV infection status and displayed dominant expression of TRAV1-2-TRAJ20. These findings have implications for understanding the role of cervical MAIT cells in health and disease.
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