The role of macrophages and T-cell apoptosis/necrosis in acute HIV-1 infection and associated gastrointestinal inflammation. (360G-Wellcome-089577_Z_09_Z)

Gastrointestinal macrophages maintain an anti-inflammatory milieu that can be destabilized by the recruitment of pro-inflammatory monocytes. HIV infection of mucosal CD4+ T cells results in massive death of these cells by apoptosis and necrosis, and these cells will be taken up by both resident and recruited macrophages. Since uptake of apoptotic and necrotic debris can activate pro-inflammatory programs in differentiating macrophages, this may set up a cycle of inflammation in the gut that may result in irreversible damage leading to long term immune activation and AIDS. Aims 1. Determine if monocyte-derived macrophages are activated by apoptotic/necrotic T-cells, both HIV infected and uninfected. 2. Determine the polarisation of macrophage activation. 3. Determine if these findings can be applied to gut-derived macrophages. 4. Determine the impact of inflammation/T-cell apoptosis on the susceptibility of macrophages to HIV-1 infection.