Towards delineating the role of dendritic cells and macrophages in SIV disease control and progression (INC9P.447)

Abstract

Abstract In HIV infection, sustained inflammation and immune activation are signature pathologies of individuals that progress to AIDS. Dendritic cells (DC) and macrophages mediate host inflammatory and antiviral responses and some evidence suggests these cells could be involved in influencing HIV disease outcome, but to what extent is unclear. Here, we longitudinally followed the kinetics of DC and macrophages in peripheral and mucosal tissues from Mamu-B*008+ rhesus macaques intrarectally infected with pathogenic SIVmac251. Mamu-B*008 is a rhesus macaque MHC class I allele highly correlated with control of SIV replication, as greater than 50% of SIV-infected Mamu-B*008+ macaques control chronic phase viral load and do not advance to disease; hence this serves as a model for controlled and progressive HIV disease in humans. We used flow cytometry to access the impact of SIV infection on DC and macrophage proportions, proliferation, and homing to lymph nodes and mucosa. Our preliminary findings reveal a divergent effect of SIV infection on each of the aforementioned DC and macrophage parameters as a function of viral load and tissue compartment. Ongoing experiments will examine the impact of SIV infection on the antigen-presenting cell properties and inflammatory nature of DC and macrophages in the context of SIV disease-progressing and -controlling hosts. These studies should provide clarity on whether DC and macrophages serve a beneficial or detrimental capacity in SIV pathogenesis.