CD4 T cells in the protection and pathogenesis of persistent Salmonella infection

Abstract

CD4 T cells contribute a diverse and non-redundant role to host defense against infections by orchestrating the activation and quality of the innate and adaptive immune responses. The diversity of CD4 T cell function is accomplished by differentiating into a plethora of distinct effector and regulatory lineages that dictate the kinetics and extent of immune activation. However, due to the range and breadth of CD4 T cell function, the precise role and mechanism of these various effector and regulatory subsets in host immunity remains incompletely understood. As persistent infections represent a significant source of morbidity and mortality worldwide, and CD4 T cells play a critical role in protection against this class of pathogens, we sought to elucidate the relative contribution of effector and regulatory CD4 T cell subsets in the pathogenesis and protection of this class of pathogens. Using a murine model of persistent Salmonella infection, we demonstrate that CD4 T cells are required for protection during primary infection but dispensable for secondary immunity. Moreover, both host and pathogen factors limit the generation of a protective effector CD4 T cell response during primary disease including increased regulatory CD4 T cell suppressive function and Salmonella-associated virulence genes, respectively, that enables establishment and persistence of disease. Together, these findings provide novel insight into disease process of persistent Salmonella infection that will aid in the design of future therapeutic and prevention strategies.