Endoplasmic reticulum stress-induced goblet cell apoptosis might contribute to intestinal barrier damage in asymptomatic people living with HIV

Objective: To investigate the role of endoplasmic reticulum stress (ERS)-related apoptotic signaling pathways in intestinal mucosal barrier dysfunction in asymptomatic people living with HIV (PLWH), with a specific focus on goblet cell apoptosis. Design: A comparative study of intestinal barrier damage in asymptomatic PLWH and healthy controls. Methods: A total of 15 asymptomatic PLWH and 15 healthy controls underwent colonoscopy, during which distal colonic mucosal biopsies were collected. Hematoxylin and eosin (H&E) staining was used to evaluate mucosal histopathology. Goblet cell apoptosis was assessed via TUNEL staining and immunofluorescence. Western blotting was performed to quantify the expression of ERS-related proteins including GRP78, p-IRE1, PERK, ATF6, CHOP, and JNK. Results: Compared to healthy controls, asymptomatic PLWH showed significant inflammatory changes in intestinal mucosa, characterized by epithelial cell shedding, reduced gland density, and inflammatory cell infiltration (P < 0.0001). Goblet cell apoptosis was significantly increased in asymptomatic PLWH group (P = 0.0081). Expression levels of ERS-related proteins GRP78, p-IRE1, PERK, ATF6, CHOP, and JNK were markedly elevated in asymptomatic PLWH group (all P < 0.01). These proteins were positively correlated with goblet cell apoptosis and negatively correlated with CD4 + T cell counts. Moreover, significant correlations were observed among key components of the ERS-related signaling pathways. Conclusion: ERS-induced apoptotic signaling pathways are likely involved in intestinal goblet cell apoptosis and mucosal barrier dysfunction in asymptomatic PLWH. These findings provide mechanistic insight into early gut pathology associated with HIV and suggest potential therapeutic targets for preserving intestinal integrity and immune homeostasis in affected individuals.