Immunity to Salmonella from a dendritic point of view

Abstract

Dendritic cells (DC) are the key link between innate and adaptive immunity. Features of DC, including their presence at sites of antigen entry, their ability to migrate from peripheral sites to secondary lymphoid organs, and their superior capacity to stimulate naïve T cells places them in this pivotal role in the immune system. DC also produce cytokines, particularly IL-12, upon antigen encounter and can thus influence the ensuing adaptive immune response. As DC are phagocytic antigen-presenting cells located at sites exposed to bacterial invaders, studies have been performed to gain insight into the role of DC in combating bacterial infections. Indeed, studies with Salmonella have shown that DC can internalize and process this bacterium for peptide presentation on MHC-II as well as MHC-I. DC can also act as bystander antigen--presenting cells by presenting Salmonella antigens after internalizing neighbouring cells that have undergone Salmonella-induced apoptotic death. DC also produce IL-12 and TNF-alpha upon Salmonella encounter. Moreover, studies in a murine infection model have shown that splenic DC increase surface expression of co-stimulatory molecules during infection, and DC contain intracellular bacteria. In addition, quantitative changes occur in splenic DC numbers in the early stages of oral Salmonella infection, and this is accompanied by redistribution of the defined DC subsets in the spleen of infected mice. DC from Salmonella-infected mice also produce cytokines and can stimulate bacteria-specific T cells upon ex vivo co-culture. In addition, DC may play a role in the traversal of bacteria from the intestinal lumen. Studying the function of DC during Salmonella infection provides insight into the capacity of this sophisticated antigen-presenting cell to initiate and modulate the immune response to bacteria.