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Updated: May 11, 2026
Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1
Published on: September 5, 2016
Intestinal macrophages display reduced permissiveness to human immunodeficiency virus 1 and decreased surface CCR5
L Li1, G Meng, M F Graham
1Division of Gastroenterology and Hepatology, Department of Medicine, University of Alabama at Birmingham, USA.
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-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.
Insights
Human immunodeficiency virus 1 (HIV-1) infects intestinal macrophages less efficiently than blood macrophages. This is due to low surface expression of the CCR5 co-receptor on intestinal cells, hindering viral entry.
Area of Science:
- Immunology
- Virology
- Gastroenterology
Background:
- The role of intestinal mononuclear cells in human immunodeficiency virus 1 (HIV-1) pathogenesis remains unclear.
- Investigating HIV-1 infection in primary intestinal macrophages is crucial for understanding disease mechanisms.
Purpose of the Study:
- To determine the biological properties of HIV-1 infection in primary intestinal macrophages.
- To elucidate the mechanisms behind HIV-1's interaction with intestinal immune cells.
Main Methods:
- Primary intestinal macrophages were isolated from the human jejunum.
- These macrophages were infected with well-characterized macrophage-tropic HIV-1 isolates.
- Viral infection was assessed by p24 antigen release, proviral DNA presence, and drug inhibition.
Main Results:
- Intestinal macrophages showed significantly reduced permissiveness to HIV-1 infection compared to peripheral blood macrophages.
- This reduced permissiveness was linked to a near absence of cell surface CCR5, a key co-receptor for HIV-1 entry.
- While both cell types had similar CCR5 mRNA levels, only blood macrophages upregulated surface CCR5 upon HIV-1 exposure.
Conclusions:
- Intestinal macrophages exhibit diminished susceptibility to HIV-1 infection.
- Impaired viral entry, primarily due to low surface CCR5 expression, underlies this reduced susceptibility.
- These findings highlight a specific immune evasion strategy by HIV-1 within the intestinal environment.
