PMID- 28262752 OWN - NLM STAT- MEDLINE DCOM- 20181106 LR - 20181113 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 DP - 2017 Mar 6 TI - Highly-Exposed HIV-1 seronegative Female Commercial Sex Workers sustain in their genital mucosa increased frequencies of tolerogenic myeloid and regulatory T-cells. PG - 43857 LID - 10.1038/srep43857 [doi] LID - 43857 AB - We and others have shown that HIV-1 highly-exposed seronegative (HESN) female commercial sex workers (CSWs) maintain low genital inflammatory conditions to prevent HIV infection. HIV-1 interacts with toll-like receptors (TLR)-7/8 to induce interferon (IFN)-alpha, an important antiviral and immunomodulatory cytokine, which act together with interleukin (IL)-10, human leukocyte antigen (HLA)-G and immunoglobulin-like transcript (ILT)-4 to initiate a "tolerogenic/regulatory" anti-inflammatory loop. In view of further unravelling elements associated with natural immunity to HIV-1, we have characterised TLR-7, IFN-alpha, IL-10, HLA-G and ILT-4 expression profiles in the genital tract of female CSWs and HIV-1-uninfected non-CSWs from Benin. Endocervical myeloid HLA-DR(+) cells from HESN CSWs expressed higher levels of IFN-alpha, TLR-7, IL-10 and HLA-G than those from both HIV-1-infected CSWs and HIV-1-uninfected non-CSWs. Further characterization of the endocervical myeloid HLA-DR(+) cells in HESN CSWs revealed a population of "tolerogenic" CD103(+) CD14(+) CD11c(+) myeloid cells expressing high levels of IFN-alpha and IL-10. Concomitantly, HESN CSWs had higher frequencies of endocervical regulatory CD4(+) T-cells when compared to those from the two other groups of women. These novel findings provide strong evidence to support the implication of tolerogenic myeloid cells expressing high levels of antiviral molecules in shaping the genital mucosal immune response to prevent HIV infection. FAU - Thibodeau, V AU - Thibodeau V AD - Laboratoire d'immunogenetique, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), Montreal, Canada. AD - Departement de Microbiologie, Infectiologie et Immunologie de l'Universite de Montreal, Montreal, Canada. FAU - Fourcade, L AU - Fourcade L AD - Laboratoire d'immunogenetique, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), Montreal, Canada. AD - Departement de Microbiologie, Infectiologie et Immunologie de l'Universite de Montreal, Montreal, Canada. FAU - Labbe, A-C AU - Labbe AC AD - Departement de Microbiologie, Infectiologie et Immunologie de l'Universite de Montreal, Montreal, Canada. FAU - Alary, M AU - Alary M AD - Centre de recherche du CHU de Quebec, Quebec, Canada. AD - Departement de medecine sociale et preventive, Universite Laval, Quebec, Canada. FAU - Guedou, F AU - Guedou F AD - Dispensaire des IST, Cotonou, Benin. FAU - Poudrier, J AU - Poudrier J AD - Laboratoire d'immunogenetique, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), Montreal, Canada. AD - Departement de Microbiologie, Infectiologie et Immunologie de l'Universite de Montreal, Montreal, Canada. FAU - Roger, M AU - Roger M AD - Laboratoire d'immunogenetique, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM), Montreal, Canada. AD - Departement de Microbiologie, Infectiologie et Immunologie de l'Universite de Montreal, Montreal, Canada. LA - eng GR - MOP-119406/CIHR/Canada PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170306 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Cytokines) SB - IM MH - Adult MH - Benin MH - Cytokines/immunology/metabolism MH - Female MH - Genitalia, Female/immunology/metabolism MH - HIV Infections/diagnosis/immunology/virology MH - HIV Seronegativity/*immunology MH - HIV-1/*immunology/physiology MH - Humans MH - Immunity, Mucosal/immunology MH - Middle Aged MH - Mucous Membrane/*immunology/metabolism MH - Myeloid Cells/*immunology/metabolism MH - Sex Work/*statistics & numerical data MH - T-Lymphocytes, Regulatory/*immunology/metabolism PMC - PMC5338327 COIS- The authors declare no competing financial interests. EDAT- 2017/03/07 06:00 MHDA- 2018/11/07 06:00 PMCR- 2017/03/06 CRDT- 2017/03/07 06:00 PHST- 2016/10/12 00:00 [received] PHST- 2017/02/01 00:00 [accepted] PHST- 2017/03/07 06:00 [entrez] PHST- 2017/03/07 06:00 [pubmed] PHST- 2018/11/07 06:00 [medline] PHST- 2017/03/06 00:00 [pmc-release] AID - srep43857 [pii] AID - 10.1038/srep43857 [doi] PST - epublish SO - Sci Rep. 2017 Mar 6;7:43857. doi: 10.1038/srep43857.