Impact on intestinal epithelial and stromal cells in people living with HIV infection.

Abstract

The gastrointestinal (GI) tract is the largest immune organ in the human body and a critical site for HIV pathology. Dysregulation of gut homeostasis and depletion of GI tissue-resident CD4+ T-cells remain permanent regardless of antiretroviral therapy (ART) and recovery of CD4+ T-cells in circulation. The irreversible depletion of GI tissue-resident CD4+ T-cells may contribute to the dysregulation of gut homeostasis by impacting intestinal stem cells (ISC) and stromal cells through impaired immune signalling. To address this question, flow cytometric analysis of duodenum, colon, and ileum pinch biopsies obtained from uninfected controls and people living with HIV (PLWH) was performed. Flow cytometric analysis of epithelial cells (CD45-EpCAM+) showed an increase in intestinal stem cells (ISC) (CD44+EpBH2+) in the colon, duodenum, and ileum of PLWH. Flow cytometric analysis of stromal cells (CD45-EpCAM-CD235a-CD38-CD19-) showed a significant change in the CD31-PDPN1+ stromal fibroblast population. Across intestinal compartments, PLWH showed increased fibroblast frequencies compared with uninfected controls that were not directly linked to CD4+ T-cell depletion in the gut or blood viremia status. Overall, these results indicate that HIV infection increases the amount of ISCs and fibroblasts in the gut, which may contribute to the overall HIV-associated dysregulation in the GI tract. Further investigation is required to determine the mechanisms by which HIV impacts nonhematopoietic cellular compartments in the gut.