Presented by: Leah Froehle
There are 37.9 million people worldwide living with HIV  and although advances in antiretroviral treatment (ART) have significantly extended life expectancy, the burden of HIV-associated comorbidities remains high [2,3,4,5]. Gut epithelial barrier disruption is a hallmark of HIV infection and even after decades of ART, markers of intestinal barrier disruption remain persistently elevated in some individuals [6,7]. Gut barrier disruption can result in the translocation of luminal bacteria and bacterial products, leading to systemic inflammation [8,9]. The specific mechanisms of this HIV-associated gut epithelial barrier disruption remain incompletely understood, but it is believed to be a critical driver of the increased prevalence of inflammation-associated comorbidities observed in those with ART-treated HIV . We demonstrated that intestinal epithelial cells from HIV-infected individuals undergo increased apoptosis in comparison to those from HIV-uninfected individuals. Employing an ex vivo 3D mini-colon organoid model cocultured with autologous colon mucosal lymphocytes, we showed that this epithelial cell death can also be seen ex vivo in HIV-infected lymphocyte-organoid co-cultures derived from HIV-uninfected individuals. Moreover, colon epithelial cell death is dependent upon tissue resident CD8+ T cells, excluding HIV-specific CD8+ T cells. We also show that CD8+ T cell derived TNF and IFN are dispensable for mediating the epithelial cell death. Since the molecular characteristics of colon tissue resident CD8+ T cells in the context of chronic viral infection are largely unknown, our current work seeks to elucidate the inherent metabolic programming of these colon tissue resident CD8+ T cells. The metabolic profile of colon tissue resident CD8+ T cells may contribute to the observed epithelial cell death in the context of HIV pathogenesis. These findings may help identify novel methods to better treat those living with HIV.
Leah Froehle – Poster Description (Audio Clip)
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