Figure 7
From: Microbial exposure alters HIV-1-induced mucosal CD4+ T cell death pathways Ex vivo
Biphasic model of LP CD4+ T cell death during acute HIV-1 infection. We theorize that in ‘early’ acute infection, prior to extensive microbial translation, pyroptotic death in bystander p24neg cells could account for the majority of LP CD4+ T cell depletion. Inflammatory mediators released during pyroptosis may contribute to epithelial barrier break down. During ‘late’ acute HIV-1 infection, T cells and APCs exposed to commensal bacteria results in enhanced HIV-1 replication, and a shift in the LP CD4+ T cell death pathway to apoptosis. The loss of Th17 cells in particular could further exacerbate epithelial barrier dysfunction and contribute to a cycle of microbial entry, T cell activation, infection and death. Increased apoptotsis from productively infected cells could also contribute to the release of apoptotic microparticles into the periphery, which others have shown could reduce the potency of early adaptive immune responses against HIV-1.