Cytokines in Salmonellosis.

Abstract

The recruitment and activation of phagocytic cells in infected tissues and the induction of T-cell- and B-cell-dependent acquired immunity are crucial for the control and resolution of Salmonella infections. These complex processes require the interaction of bacteria with a multitude of cell surface receptors and the controlled production of soluble mediators. The mechanisms of cytokine induction in response to Salmonella and the role of cytokine networks in Salmonella infections are the main foci of this review. Pathogen-associated molecular pattern receptors play an important role in recognition of bacteria by the host. Effective immunity against the bacterium therefore relies on the ability of the host to recruit phagocytes in the tissues and to enhance the antibacterial functions of these inflammatory cells. TNF-a, IFN-?, IL12, IL15, and IL18 are needed for the full expression of innate host resistance to Salmonella. The genes for mammalian cytokines can be cloned into suitable vectors and expressed in Salmonella as functional proteins. The in vivo production of cytokines by Salmonella carriers can have therapeutic applications and can modulate immune functions in the host. The possibility to modulate antigen-specific immune responses by expressing cytokines in Salmonella is illustrated by the increase in Salmonella-specific IgA responses induced by administration of IL-5-expressing bacteria. The same cytokines that are responsible for endotoxic shock are elevated in the late stages of lethal Salmonella infections, indicating that the toxicity of Salmonella lipopolysaccharide (LPS) may actually be contributing to the death of the host.