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Journal of Virology, April 2009, p. 3258-3267, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.01796-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Macrophages in Vaginal but Not Intestinal Mucosa Are Monocyte-Like and Permissive to Human Immunodeficiency Virus Type 1 Infection{triangledown}

Ruizhong Shen,1 Holly E. Richter,2 Ronald H. Clements,3 Lea Novak,4 Kayci Huff,1 Diane Bimczok,1 Sumathi Sankaran-Walters,5 Satya Dandekar,5 Paul R. Clapham,6 Lesley E. Smythies,1 and Phillip D. Smith1,7*

Departments of Medicine (Gastroenterology),1 Obstetrics and Gynecology,2 Surgery (Gastrointestinal),3 Pathology, University of Alabama at Birmingham, Birmingham, Alabama,4 Department of Medical Microbiology and Immunology, University of California School of Medicine, Davis, California,5 Program in Molecular Medicine and Department of Molecular Genetics and Microbiology, University of Massachusetts, Worcester, Massachusetts,6 VA Medical Center, Birmingham, Alabama7

Received 27 August 2008/ Accepted 6 January 2009

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.

* Corresponding author. Mailing address: University of Alabama at Birmingham, 610 SHEL, 1825 University Blvd., Birmingham, AL 35294. Phone: (205) 975-9254. Fax: (205) 996-9113. E-mail: pdsmith{at}uab.edu

{triangledown} Published ahead of print on 19 January 2009.

Journal of Virology, April 2009, p. 3258-3267, Vol. 83, No. 7
0022-538X/09/$08.00+0     doi:10.1128/JVI.01796-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Perez, L. G., Costa, M. R., Todd, C. A., Haynes, B. F., Montefiori, D. C. (2009). Utilization of Immunoglobulin G Fc Receptors by Human Immunodeficiency Virus Type 1: a Specific Role for Antibodies against the Membrane-Proximal External Region of gp41. J. Virol. 83: 7397-7410 [Abstract] [Full Text]  


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