Macrophage accumulation in gut mucosa differentiates AIDS from chronic SIV infection in rhesus macaques
Zachary D Swan1,2, Elizabeth R Wonderlich1,2, Simon M Barratt-Boyes1,3,2
1Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA.
Abstract:
The relationship between recruitment of mononuclear phagocytes to lymphoid and gut tissues and disease in HIV and SIV infection remains unclear. To address this question, we conducted cross-sectional analyses of dendritic cell (DC) subsets and CD163(+) macrophages in lymph nodes (LNs) and ileum of rhesus macaques with acute and chronic SIV infection and AIDS. In LNs significant differences were only evident when comparing uninfected and AIDS groups, with loss of myeloid DCs and CD103(+) DCs from peripheral and mesenteric LNs, respectively, and accumulation of plasmacytoid DCs and macrophages in mesenteric LNs. In contrast, there were fourfold more macrophages in ileum lamina propria in macaques with AIDS compared with chronic infection, and this increased to 40-fold in Peyer's patches. Gut macrophages exceeded plasmacytoid DCs and CD103(+) DCs by ten- to 17-fold in monkeys with AIDS but were at similar low frequencies as DCs in chronic infection. Gut macrophages in macaques with AIDS expressed IFN-α and TNF-α consistent with cell activation. CD163(+) macrophages also accumulated in gut mucosa in acute infection but lacked expression of IFN-α and TNF-α. These data reveal a relationship between inflammatory macrophage accumulation in gut mucosa and disease and suggest a role for macrophages in AIDS pathogenesis.
Insights
Mononuclear phagocyte accumulation in the gut, particularly inflammatory macrophages, is linked to simian immunodeficiency virus (SIV) disease progression. This suggests a key role for these cells in acquired immunodeficiency syndrome (AIDS) pathogenesis.
Area of Science:
- Immunology
- Virology
- Pathogenesis
Background:
- The role of mononuclear phagocytes in HIV/SIV infection pathogenesis is not fully understood.
- Investigating immune cell dynamics in lymphoid and gut tissues is crucial for understanding disease progression.
Purpose of the Study:
- To analyze dendritic cell (DC) subsets and CD163(+) macrophages in lymph nodes and ileum during acute, chronic, and AIDS stages of SIV infection in rhesus macaques.
- To elucidate the relationship between immune cell recruitment and disease severity in SIV infection.
Main Methods:
- Cross-sectional analysis of immune cell populations in lymph nodes and ileum.
- Quantification of dendritic cell subsets and CD163(+) macrophages.
- Assessment of cytokine expression (IFN-α, TNF-α) in macrophages.
Main Results:
- Significant changes in lymph node immune cells were observed between uninfected and AIDS groups, including loss of myeloid and CD103(+) DCs and accumulation of plasmacytoid DCs and macrophages.
- Macrophage populations increased dramatically in the gut lamina propria and Peyer's patches of macaques with AIDS compared to chronic infection.
- Activated macrophages expressing IFN-α and TNF-α were found in the gut mucosa of macaques with AIDS.
Conclusions:
- Inflammatory macrophage accumulation in the gut mucosa is associated with SIV disease progression.
- Macrophages play a significant role in the pathogenesis of acquired immunodeficiency syndrome (AIDS).
- Gut immune responses involving macrophages may be critical in managing SIV/HIV infection.
