Macrophages in vaginal but not intestinal mucosa are monocyte-like and permissive to human immunodeficiency virus type 1 infection

R Shen, HE Richter, RH Clements, L Novak… - Journal of …, 2009 - Am Soc Microbiol
R Shen, HE Richter, RH Clements, L Novak, K Huff, D Bimczok, S Sankaran-Walters…
Journal of virology, 2009Am Soc Microbiol
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 …
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.
American Society for Microbiology