Pulmonary macrophage alterations associated with aging and SIV infection in rhesus macaques (VIR9P.1155)

Abstract

Abstract Accelerated aging occurs in HIV-infected persons HIV, despite ART, as seen by earlier onset of chronic inflammatory diseases and HIV-associated non-AIDS (HANA) conditions than in non-HIV-infected individuals. In the rhesus macaque SIV model, we reported earlier that increasing monocyte turnover associated with tissue macrophage death predicted onset of terminal disease progression. Here, we hypothesize that macrophage dysregulation contributes to accelerated aging that occurs during SIV infection. We compared macrophage populations of the lung in older and younger uninfected and SIV-infected rhesus macaques. We observed that the ratio of alveolar macrophages (AM) to interstitial macrophages (IM) was significantly lower in chronic SIV-infected younger macaques and older uninfected monkeys compared to uninfected young macaques. The mechanisms differed, however, because the lower ratio in the older uninfected monkeys was due to lower numbers of AM while the shift during SIV infection of younger adults was due to increasing numbers of IM. Functionally, AM of older vs younger uninfected animals exhibited higher levels of pro-inflammatory cytokine secretion (TNFα, IL12) during incubation in medium yet produced lower levels of cytokines after induction with LPS ex vivo. During the acute phase of SIV infection, we observed a higher turnover of monocytes and IM in older compared to younger macaques. This suggests that AM become dysregulated during aging and SIV/HIV infection.