title: Mucosal innate immune factors in the female genital tract are associated with vaginal HIV-1 shedding independent of plasma viral load.
abstract: Recent studies indicate that mucosal innate immune factors modulate HIV-1 infection in vitro. Our interest was to examine the levels of innate mucosal factors for their potential association with HIV-1 shedding in the female genital tract. Vaginal lavages were collected from HIV-1-infected women who had vaginal viral loads (VVL) that were below, within, or above the 90% confidence interval (CI) predicted by their matched plasma viral loads. Innate immune factors [cathepsin D, lactoferrin (Lf), myeloid related protein (MRP)-8, MRP-8/14, secretory leukocyte protease inhibitor, and gp340], cytokines (IL-1beta and TNF-alpha), and chemokines (MIP-1alpha, MIP-1beta, RANTES, and SDF-1alpha) were quantified by ELISA. Leukocyte levels were determined using a leukocyte reagent strip for urinalysis. Lf, MRP-8/14, gp340, and IL-1beta levels were significantly higher in vaginal lavages above the 90% CI and generally correlated with each other and with VVL. Leukocyte levels were significantly higher in the lavages that had virus shedding above the 90% CI and correlated strongly with Lf levels and VVL. In this group of women, these results suggest that the levels of certain innate immune factors are more closely associated with HIV-1 shedding in the genital mucosa than plasma virus concentrations.
authors.affiliation: Laboratory Branch, Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. cummins@sri.org
authors.forename: James E
authors.initials: JE
authors.lastname: Cummins
authors.forename: Logan
authors.initials: L
authors.lastname: Christensen
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Lennox
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bush
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wu
authors.forename: Daniel
authors.initials: D
authors.lastname: Malamud
authors.forename: Tammy
authors.initials: T
authors.lastname: Evans-Strickfaden
authors.forename: Aladin
authors.initials: A
authors.lastname: Siddig
authors.forename: Angela M
authors.initials: AM
authors.lastname: Caliendo
authors.forename: Clyde E
authors.initials: CE
authors.lastname: Hart
authors.forename: Charlene S
authors.initials: CS
authors.lastname: Dezzutti
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D018925:Chemokines / Q000032:analysis; D016009:Chi-Square Distribution; D016207:Cytokines / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology; D007155:Immunologic Factors / Q000032:analysis; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D014621:Vagina / Q000276:immunology* / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000821:virology; D017201:Virus Shedding / Q000276:immunology*
chemical_list: D018925:Chemokines; D016207:Cytokines; D007155:Immunologic Factors; D012367:RNA, Viral