Macrophages in vaginal but not intestinal mucosa are monocyte-like and permissive to human immunodeficiency virus type 1 infection.
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.
Shen
Ruizhong
R
Department of Medicine (Gastroenterology), University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Richter
Holly E
HE
Clements
Ronald H
RH
Novak
Lea
L
Huff
Kayci
K
Bimczok
Diane
D
Sankaran-Walters
Sumathi
S
Dandekar
Satya
S
Clapham
Paul R
PR
Smythies
Lesley E
LE
Smith
Phillip D
PD
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*
D015703:Antigens, CD; D015728:Receptors, HIV