The MAIT cell response to controlled oral enterotoxigenic E. coli challenge

Area of Science:

• Immunology
• Microbiology
• Gastroenterology

Background:

• Mucosal-associated invariant T (MAIT) cells are crucial for barrier immunity, recognizing microbial antigens via MR1 molecules.
• Enterotoxigenic E. coli (ETEC) is a significant cause of diarrheal illness globally, especially in vulnerable populations.
• The role of MAIT cells in ETEC infection remains largely unexplored.

Purpose of the Study:

• To investigate the dynamic response of MAIT cells during ETEC infection in a human challenge model.
• To correlate MAIT cell activation, functionality, and expansion with ETEC infection severity.

Main Methods:

• Utilized a controlled human ETEC challenge model with strains H10407 and B7A.
• Analyzed peripheral blood samples at multiple time points post-challenge.
• Assessed MAIT cell phenotype, function, proliferation, and homing potential (CCR9, α4β7) at protein and transcriptional levels.

Main Results:

• MAIT cells showed increased activation, functionality, and proliferation by day 7 post-challenge, particularly in individuals with moderate-to-severe diarrhea (MSD).
• Elevated CCR9 and α4β7 expression in MSD-positive individuals indicated enhanced gut homing.
• A significant expansion of the peripheral MAIT cell pool was observed 28 days post-challenge, correlating with disease severity on day 7.

Conclusions:

• MAIT cells mount a systemic response, including activation and expansion, to ETEC infection.
• The magnitude of the MAIT cell response is associated with the development and severity of symptomatic ETEC disease.
• MAIT cells are implicated as important contributors to the host's defense and disease pathology during ETEC infections.