HIV-Exposed Seronegative Sex Workers Express Low T-Cell Activation and an Intact Ectocervical Tissue MicroenvironmentKarolinska Inst, Ctr Mol Med, Karolinska Univ Hosp, Dept Infect Dis,Dept Med Solna,Div Infect Dis, S-17164 Stockholm, Sweden..
Karolinska Inst, Ctr Mol Med, Karolinska Univ Hosp, Dept Infect Dis,Dept Med Solna,Div Infect Dis, S-17164 Stockholm, Sweden..
Karolinska Inst, Ctr Mol Med, Karolinska Univ Hosp, Dept Infect Dis,Dept Med Solna,Div Infect Dis, S-17164 Stockholm, Sweden..
Univ Nairobi, Dept Med Microbiol, Nairobi 00100, Kenya..
Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB R3A 1R9, Canada..
Karolinska Inst, Ctr Mol Med, Karolinska Univ Hosp, Dept Infect Dis,Dept Med Solna,Div Infect Dis, S-17164 Stockholm, Sweden..
Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA..
Univ Nairobi, Dept Med Microbiol, Nairobi 00100, Kenya..
Univ Nairobi, Dept Med Microbiol, Nairobi 00100, Kenya.;Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB R3A 1R9, Canada.;Partners Hlth & Dev Africa, Nairobi 00100, Kenya..
Univ Nairobi, Dept Med Microbiol, Nairobi 00100, Kenya.;Univ Manitoba, Dept Med Microbiol & Infect Dis, Winnipeg, MB R3A 1R9, Canada.;Partners Hlth & Dev Africa, Nairobi 00100, Kenya.;Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB R3A 1R9, Canada..
Karolinska Inst, Ctr Mol Med, Karolinska Univ Hosp, Dept Infect Dis,Dept Med Solna,Div Infect Dis, S-17164 Stockholm, Sweden..
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2021 (English)In: Vaccines, E-ISSN 2076-393X, Vol. 9, no 3, article id 217Article in journal (Refereed) Published
Abstract [en]
Immunological correlates of natural resistance to HIV have been identified in HIV-exposed seronegative (HESN) individuals and include a low-inflammatory genital mucosal status. The cervicovaginal epithelium has not been studied for such correlates despite constituting an important barrier against sexual HIV transmission. To fill this gap in knowledge, we collected samples of blood, cervical mononuclear cells, cervicovaginal lavage, and ectocervical tissue from Kenyan HESN sex workers (n = 29) and controls (n = 33). The samples were analyzed by flow cytometry, protein profiling, 16S rRNA gene sequencing, in situ image analysis, and tissue-based RNA sequencing. A significantly higher relative proportion of regulatory T cells in blood (B7(+)CD25(hi)FoxP3(+)CD127(lo)CD4(+) and B7(+)Helios(+)FoxP3(+)CD4(+)), and a significantly lower proportion of activated cervical T cells (CCR5(+)CD69(+)CD4(+) and CCR5(+)CD69(+)CD8(+)), were found in the HESN group compared with the controls. In contrast, there were no statistically significant differences between the study groups in cervicovaginal protein and microbiome compositions, ectocervical epithelial thickness, E-cadherin expression, HIV receptor expression, and tissue RNA transcriptional profiles. The identification of an intact ectocervical microenvironment in HESN individuals add new data to current knowledge about natural resistance to sexual transmission of HIV.
Place, publisher, year, edition, pages
MDPI AG , 2021. Vol. 9, no 3, article id 217
Keywords [en]
HIV, mucosa, female genital tract, RNA sequencing, microbiome, image analysis, protein profiling, HIV-exposed seronegative, HESN
National Category
Basic Medicine
Identifiers
URN: urn:nbn:se:kth:diva-293160DOI: 10.3390/vaccines9030217ISI: 000634199500001PubMedID: 33806390Scopus ID: 2-s2.0-85102717353OAI: oai:DiVA.org:kth-293160DiVA, id: diva2:1545825
Note
QC 20210420
2021-04-202021-04-202022-06-25Bibliographically approved