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

Ruizhong Shen, Holly E. Richter, Ronald H. Clements, Lea Novak, Kayci Huff, Diane Bimczok, Sumathi Sankaran-Walters, Satya Dandekar, Paul R. Clapham, Lesley E. Smythies, Phillip D. Smith

Research output: Contribution to journalArticlepeer-review

136 Scopus citations


Mucosal surfaces play a major role in human immunodeficiency virus type 1 (HTV-1) transmission and pathogenesis, and yet the role of lamina propria macrophages in mucosal HTV-1 infection has received little investigative attention. We report here that vaginal and intestinal macrophages display distinct phenotype and HTV-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 HTV-1 pathogenesis and that vaginal macrophages play a previously underappreciated but potentially important role in mucosal HTV-1 infection in the female genital tract.

Original languageEnglish (US)
Pages (from-to)3258-3267
Number of pages10
JournalJournal of Virology
Issue number7
StatePublished - Apr 2009

ASJC Scopus subject areas

  • Immunology
  • Virology


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