Colitis-Induced Th17 Cells Increase the Risk for Severe Subsequent Clostridium difficile Infection

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Clostridium difficile infection (CDI) is a leading hospital-acquired infection.
• CDI is notably more common and severe in patients with inflammatory bowel disease (IBD).

Purpose of the Study:

• To investigate the mechanisms by which prior colitis exacerbates CDI.
• To identify the immune cells and factors involved in this heightened susceptibility.

Main Methods:

• Mice with dextran sulfate sodium (DSS)-induced colitis were allowed to recover before C. difficile infection.
• Adoptive transfer of Th17 cells was performed in naive mice.
• Analysis of mortality, CDI severity, and cytokine levels (IL-6, IL-23, IL-17) in mice and humans.

Main Results:

• DSS-treated mice exhibited increased mortality and CDI severity compared to controls.
• Severe CDI was dependent on CD4+ T cells that persisted post-colitis.
• Adoptive transfer of Th17 cells increased CDI-associated mortality via IL-17.
• Elevated IL-6 and IL-23 levels correlated with severe CDI in humans, with high IL-6 predicting increased mortality.

Conclusions:

• Th17 cells play a crucial role in the pathogenesis of CDI following colitis.
• Persistent Th17 cells contribute to exacerbated CDI.
• Th17 cells and their associated cytokines represent potential therapeutic targets for preventing severe CDI.