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

OBJECTIVE

To investigate the role of endoplasmic reticulum stress (ERS)-related apoptotic signaling pathways in intestinal mucosal barrier dysfunction in asymptomatic people with HIV (PWH), with a specific focus on goblet cell apoptosis.

DESIGN

A comparative study of intestinal barrier damage in asymptomatic PWH and healthy controls.

METHODS

A total of 15 asymptomatic PWH 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 PWH 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 PWH group ( P = 0.0081). Expression levels of ERS-related proteins GRP78, p-IRE1, PERK, ATF6, CHOP, and JNK were markedly elevated in asymptomatic PWH 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 PWH. 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.