Intestinal macrophages display reduced permissiveness to human immunodeficiency virus 1 and decreased surface CCR5.
OBJECTIVE
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-tropic isolates of HIV-1 (ADA, DJV, and Ba-L).


RESULTS
Productive HIV-1 infection of intestinal macrophages was demonstrated by the release of p24 antigen, the presence of proviral DNA, and zidovudine inhibition of infection. Surprisingly, the titer of virus needed to establish infection of intestinal macrophages 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 or differences in CD4 expression. Instead, intestinal macrophages expressed almost no CCR5, the principal coreceptor for macrophage-tropic HIV-1, compared with blood-derived macrophages, although both cell types contained comparable levels of CCR5 messenger RNA. Exposure of blood-derived but not intestinal 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.
Li
L
L
Division of Gastroenterology and Hepatology, Department of Medicine, University of Alabama at Birmingham, USA.
Meng
G
G
Graham
M F
MF
Shaw
G M
GM
Smith
P D
PD
D015704:CD4 Antigens / Q000378:metabolism; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000821:virology*; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000378:metabolism; D012367:RNA, Viral / Q000378:metabolism; D019713:Receptors, CCR5 / Q000378:metabolism*; D013997:Time Factors; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology; D015215:Zidovudine / Q000494:pharmacology
D015704:CD4 Antigens; D016655:HIV Core Protein p24; D012367:RNA, Viral; D019713:Receptors, CCR5; D015215:Zidovudine; D010450:Endopeptidases; C023139:dispase