title: Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota.
abstract: Cervical human papillomavirus (HPV) infection may increase HIV risk. Since other genital infections enhance HIV susceptibility by inducing inflammation, we assessed the impact of HPV infection and clearance on genital immunology and the cervico-vaginal microbiome. Genital samples were collected from 65 women for HPV testing, immune studies and microbiota assessment; repeat HPV testing was performed after 6 months. All participants were HIV-uninfected and free of bacterial STIs. Cytobrush-derived T cell and dendritic cell subsets were assessed by multiparameter flow cytometry. Undiluted cervico-vaginal secretions were used to determine cytokine levels by multiplex ELISA, and to assess bacterial community composition and structure by 16S rRNA gene sequence analysis. Neither HPV infection nor clearance were associated with broad differences in cervical T cell subsets or cytokines, although HPV clearance was associated with increased Langerhans cells and HPV infection with elevated IP-10 and MIG. Individuals with HPV more frequently had a high diversity cervico-vaginal microbiome (community state type IV) and were less likely to have an L. gasseri predominant microbiome. In summary, HPV infection and/or subsequent clearance was not associated with inflammation or altered cervical T cell subsets, but associations with increased Langerhans cells and the composition of the vaginal microbiome warrant further exploration.
authors.affiliation: Departments of Medicine, University of Toronto, Toronto, Ontario, Canada.|Departments of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Shannon
authors.affiliation: Departments of Medicine, University of Toronto, Toronto, Ontario, Canada.|Departments of Immunology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: T J
authors.initials: TJ
authors.lastname: Yi
authors.affiliation: Public Health Ontario-Toronto Public Health Laboratory, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Perusini
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: P
authors.initials: P
authors.lastname: Gajer
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: B
authors.initials: B
authors.lastname: Ma
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Humphrys
authors.affiliation: Women's Health in Women's Hands Community Health Centre, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Thomas-Pavanel
authors.affiliation: Women's Health in Women's Hands Community Health Centre, Toronto, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Chieza
authors.affiliation: Women's Health in Women's Hands Community Health Centre, Toronto, Ontario, Canada.
authors.forename: P
authors.initials: P
authors.lastname: Janakiram
authors.affiliation: Women's Health in Women's Hands Community Health Centre, Toronto, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Saunders
authors.affiliation: Women's Health in Women's Hands Community Health Centre, Toronto, Ontario, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Tharao
authors.affiliation: Departments of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Huibner
authors.affiliation: Departments of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Shahabi
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, USA.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: J
authors.initials: J
authors.lastname: Ravel
authors.affiliation: Public Health Ontario-Toronto Public Health Laboratory, Toronto, Ontario, Canada.|Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Rebbapragada
authors.affiliation: Departments of Medicine, University of Toronto, Toronto, Ontario, Canada.|Departments of Immunology, University of Toronto, Toronto, Ontario, Canada.|University Health Network, Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Kaul
mesh_terms: D000328:Adult; D054357:Chemokine CXCL10 / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology / Q000382:microbiology*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology*; D064307:Microbiota / Q000235:genetics*; D008875:Middle Aged; D012336:RNA, Ribosomal, 16S / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000821:virology; D014621:Vagina / Q000276:immunology* / Q000382:microbiology; D019562:Viral Load
chemical_list: C114753:CXCL10 protein, human; C080810:CXCL9 protein, human; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D016207:Cytokines; D012336:RNA, Ribosomal, 16S