Macrophages are important for linking the transition from innate to adaptive immunity and also are targeted for infection by SIV and HIV. Unlike most other lentiviruses, HIV and SIV have gained the ability to also infect CD4+ T cells, which likely dramatically affected the concepts about pathogenesis. Thus, while HIV and SIV appear to more overtly impact CD4+ T cells, it is relevant that much effort is made by the immune system to retain the macrophage-mediated effects of HIV and SIV that remain relevant and substantial. This was further demonstrated by the dramatic increase in blood monocyte turnover rates for producing monocytes to replace the tissue macrophages destroyed by the virus. In essence, the increased monocyte turnover appears to better predict progression to AIDS than declining levels of CD4+ T cells and further provides direct evidence that macrophages, in addition to, or instead of CD4+ T cells, play a role in the development of AIDS during HIV infection.
These findings help explain why damage to this arm of the innate immune system was not previously reported and, more importantly, why the manifestation of AIDS following HIV infection may be delayed in some individuals despite the presence of a high viral load and low CD4+ T cell count. Recent data also showed that specific lung macrophage populations play distinct roles in the pathogenesis of pulmonary disease during SIV infection. For example, results suggest that short-lived macrophages contribute to AIDS pathogenesis whereas long-lived macrophages may contribute to establishing a long-term virus reservoir and promoting chronic inflammation. Work also demonstrated a decline in neutrophil production and earlier release from bone marrow during aging, despite increasing plasma G-CSF levels in rhesus macaques. Studies continue to examine the roles of macrophages and neutrophils in the mechanisms of aging, rapid disease progression in pediatric and geriatric AIDS, pathogenesis of lung and heart disease in AIDS, establishment of virus reservoirs, approaches to remove the viral reservoirs, and mechanisms in the reactivation of TB using the TB/SIV co-infection model.
