Protective host immune responses to Salmonella infection

Abstract

Salmonella enterica serovars Typhi and Paratyphi are the causative agents of human typhoid fever. Current typhoid vaccines are ineffective and are not widely used in endemic areas. Greater understanding of host-pathogen interactions during Salmonella infection should facilitate the development of improved vaccines to combat typhoid and nontyphoidal Salmonellosis. This review will focus on our current understanding of Salmonella pathogenesis and the major host immune components that participate in immunity to Salmonella infection. In addition, recent findings regarding host immune mechanisms in response to Salmonella infection will be also discussed, providing a new perspective on the utility of improved tools to study the immune response to Salmonella infections.

Keywords: B cells; CD4 T cells; bacterial infection; immunity; protection.

Figure 1. The role of noncognate T-cell activation in Salmonella immunity

During primary infection of Salmonella, dendritic cells present antigens to naive CD4 T cells causing expansion of a pool of Salmonella-specific Th1 cells. These Th1 cells can acquire the ability to produce the effector cytokine IFN-γ and migrate to infected tissues where they can be stimulated in a cognate fashion through TCR ligation by MHC:peptide complexes expressed on infected cells (top, antigen/Salmonella). In addition, these Th1 cells have the capacity to be stimulated by signals elicited by PAMPs (middle, PAMPs/salmonella) and may also be able to respond to co-infection with other pathogens (bottom, PAMPs/other pathogens).