Evidence of Intestinal Barrier Dysfunction in Asymptomatic HIV Infection via the NLRP3/Caspase-1/GSDMD Pyroptosis...

Area of Science:

• Immunology
• Gastroenterology
• Infectious Diseases

Background:

• Intestinal barrier dysfunction is an early hallmark of HIV infection.
• The precise mechanisms driving this dysfunction remain largely unknown.

Purpose of the Study:

• To investigate the role of the NLRP3/Caspase-1/GSDMD pyroptosis pathway in intestinal barrier disruption in asymptomatic HIV infection.

Main Methods:

• The study compared intestinal mucosal abnormalities, pyroptosis markers, tight junction proteins, inflammatory cytokines, and microbial translocation in 20 asymptomatic people living with HIV (PLWH) and 15 matched controls.

Main Results:

• PLWH showed mucosal abnormalities, increased NLRP3/Caspase-1/GSDMD-NT, decreased Occludin and ZO-1, and elevated IL-1β, IL-18, and LPS.
• NLRP3 activation correlated negatively with tight junction proteins (Occludin/ZO-1) and positively with LPS.
• Lower CD4+ T-cell counts were associated with increased inflammasome activation.

Conclusions:

• Intestinal barrier disruption in early HIV infection is associated with NLRP3-mediated pyroptosis.
• This pathway may contribute to early epithelial injury and microbial translocation.
• Targeting the NLRP3 inflammasome presents a potential therapeutic strategy for HIV-associated gut pathology.