Intestinal macrophages display reduced permissiveness to human immunodeficiency virus 1 and decreased surface CCR5

Background & Aims: Because the role of intestinal mononuclear cells in the pathogenesis of human immunodeficiency virus 1 (HIV-1) disease has not been elucidated, we determined the biological properties of HIV-1 infection in primary intestinal macrophages, Methods: Mucosal macrophages purified from normal human jejunum were infected with well-characterized macrophage-tropi c isolates of HIV-1 (ADA, DJV, and Ba-L), Results: Productive HIV-1 infecti on of intestinal macrophages was demonstrated by the release of p24 antigen , the presence of proviral DNA, and zidovudine inhibition of infection. Sur prisingly, the titer of virus needed to establish infection of intestinal m acrophages was 100-1000-fold higher than that required to infect peripheral blood derived macrophages. This marked reduction in the permissiveness of intestinal macrophages to HIV-1 was not caused by the isolation procedure o r differences in CD4 expression. Instead, intestinal macrophages expressed almost no CCR5, the principal coreceptor for macrophage-tropic HIV-1, compa red with blood-derived macrophages, although both cell types contained comp arable levels of CCR5 messenger RNA. Exposure of blood-derived but not inte stinal macrophages to HIV-1 or gp120 led to increased surface expression of CCR5. Conclusions: Intestinal macrophages express reduced levels of HIV-1, probably because of impaired permissiveness to HIV-1 entry associated with the near absence of cell surface CCR5.