title: Macrophages in vaginal but not intestinal mucosa are monocyte-like and permissive to human immunodeficiency virus type 1 infection.
abstract: Mucosal surfaces play a major role in human immunodeficiency virus type 1 (HIV-1) transmission and pathogenesis, and yet the role of lamina propria macrophages in mucosal HIV-1 infection has received little investigative attention. We report here that vaginal and intestinal macrophages display distinct phenotype and HIV-1 permissiveness profiles. Vaginal macrophages expressed the innate response receptors CD14, CD89, CD16, CD32, and CD64 and the HIV-1 receptor/coreceptors CD4, CCR5, and CXCR4, similar to monocytes. Consistent with this phenotype, green fluorescent protein-tagged R5 HIV-1 entered macrophages in explanted vaginal mucosa as early as 30 min after inoculation of virus onto the epithelium, and purified vaginal macrophages supported substantial levels of HIV-1 replication by a panel of highly macrophage-tropic R5 viruses. In sharp contrast, intestinal macrophages expressed no detectable, or very low levels of, innate response receptors and HIV-1 receptor/coreceptors and did not support HIV-1 replication, although virus occasionally entered macrophages in intestinal tissue explants. Thus, vaginal, but not intestinal, macrophages are monocyte-like and permissive to R5 HIV-1 after the virus has translocated across the epithelium. These findings suggest that genital and gut macrophages have different roles in mucosal HIV-1 pathogenesis and that vaginal macrophages play a previously underappreciated but potentially important role in mucosal HIV-1 infection in the female genital tract.
authors.affiliation: Department of Medicine (Gastroenterology), University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Ruizhong
authors.initials: R
authors.lastname: Shen
authors.forename: Holly E
authors.initials: HE
authors.lastname: Richter
authors.forename: Ronald H
authors.initials: RH
authors.lastname: Clements
authors.forename: Lea
authors.initials: L
authors.lastname: Novak
authors.forename: Kayci
authors.initials: K
authors.lastname: Huff
authors.forename: Diane
authors.initials: D
authors.lastname: Bimczok
authors.forename: Sumathi
authors.initials: S
authors.lastname: Sankaran-Walters
authors.forename: Satya
authors.initials: S
authors.lastname: Dandekar
authors.forename: Paul R
authors.initials: PR
authors.lastname: Clapham
authors.forename: Lesley E
authors.initials: LE
authors.lastname: Smythies
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Smith
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D005260:Female; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D007413:Intestinal Mucosa / Q000821:virology*; D008264:Macrophages / Q000737:chemistry / Q000821:virology*; D009924:Organ Culture Techniques; D015728:Receptors, HIV / Q000032:analysis; D014621:Vagina / Q000821:virology*
chemical_list: D015703:Antigens, CD; D015728:Receptors, HIV