Mechanisms of cholera toxin in the modulation of T<inf>H</inf>17 responses

Numerous studies have shown that T<inf>H</inf>17 cells and their signature cytokine IL-17A are critical to host defense against various bacterial and fungal infections. The protective responses mediated by T<inf>H</inf>17 cells and IL- 17A include the recruitment of neutrophils, release of antimicrobial peptides and chemokines, and enhanced tight junction of epithelial cells. Due to the importance of T<inf>H</inf>17 cells in infections, efforts have been made to develop T<inf>H</inf>17-based vaccines. The goal of vaccination is to establish a protective immunological memory. Most currently approved vaccines are antibody-based and have limited protection against stereotypically different strains. Studies show that T-cell–based vaccines may overcome this limitation and protect hosts against infection of different strains. Two main strategies are used to develop T<inf>H</inf>17 vaccines: identification of T<inf>H</inf>17-specific antigens and T<inf>H</inf>17-skewing adjuvants. Studies have revealed that cholera toxin (CT) induces a potent T<inf>H</inf>17 response following vaccination. Antigen vaccination along with CT induces a robust T<inf>H</inf>17 response, which is sometimes accompanied by T<inf>H</inf>1 responses. Due to the toxicity of CT, it is hard to apply CT in a clinical setting. Thus, understanding how CT modulates T<inf>H</inf>17 responses may lead to the development of successful T<inf>H</inf>17-based vaccines.