T Follicular Helper Cells Regulate Humoral Response for Host Protection against Intestinal Citrobacter rodentium Infection.

Citrobacter rodentium colonizes at the colon and causes mucosal inflammation in mice. Previous studies have revealed the importance of the innate and adaptive immune response for controlling C. rodentium infection. In the present study, we examined the role of T follicular helper (Tfh) cells in intestinal C. rodentium infection using mice with Bcl6 deficiency in T cells. Tfh cells were absolutely required at the late, but not the early, phase to control infection. Compared with control mice, we observed systemic pathogen dissemination and more severe colitis in Tfh-deficient mice. Furthermore, the susceptibility of Tfh-deficient mice correlated with an impaired serum IgG1 response to infection, and serum Abs from infected wild-type mice protected Tfh-deficient mice from infection. The transfer of wild-type Tfh cells also restored the levels of IgG1 and led to effective clearance of the pathogens in Tfh-deficient mice. Moreover, during C. rodentium infection, IL-21- and IL-4-producing Tfh cells were increased obviously in wild-type mice, correlating with IgG1 as the major isotype in germinal center B cells. Taken together, our work highlights the requirement and the function of Tfh cells in regulating humoral response for the host protection against C. rodentium infection.