Lamina propria lymphocytes, not macrophages, express CCR5 and CXCR4 and are the likely target cell for human immunodeficiency virus type 1 in the intestinal mucosa

Most human immunode®ciency virus type 1 (HIV-1) infections are acquired via mucosal surfaces, and transmitted viruses are nearly always macrophage-tropic, suggesting that mu-cosal macrophages participate in early HIV-1 infection. Mucosal lymphocytes isolated from normal human intestine expressed CD4 ( antibody-binding sites [ABSs]/cell),14,530 5 7970 CCR5 ( ABSs/cell), and CXCR4 ( ABSs/cell), but intestinal macro-2730 5 1524 2507 5 1840 phages, which also expressed CD4 ( ABSs/cell), displayed no detectable CCR52959 5 2695 or CXCR4 ABS. The absence of CCR5 on intestinal macrophages was not due to expression of the D32 deletion allele because matched-blood monocytes expressed CCR5. CCR5+CXCR4+ intestinal lymphocytes supported both R5 (BaL) and X4 (IIIB) HIV-1 replication, whereas the CCR52CXCR42 macrophages were not permissive to either isolate or other laboratory isolates (ADA and DJV) and primary isolates (MDR 24 and JOEL). In the intestinal mucosa, lymphocytes, not macrophages, are the likely target cell for R5 (and X4) HIV-1 and are the major source of HIV-1 production during early infection. Mucosal surfaces are the most common route of human im-munode®ciency virus type 1 (HIV-1) entry into the body. Viru