Salmonella infection: Interplay between the bacteria and host immune system

Abstract

Salmonella infection causes morbidity and mortality throughout the world with the host immune response varying depending on whether the infection is acute and limited, or systemic and chronic. Additionally, Salmonella bacteria have evolved multiple mechanisms to avoid or subvert immunity to its own benefit and often the anatomical location of infection plays a role in both the immune response and bacterial fate. Here, we provide an overview of the interplay between the immune system and Salmonella, while discussing how different host and bacterial factors influence the outcome of infection.

Keywords: B cell; Dendritic cell; Immunomodulation; Infectious disease; Macrophage; Neutrophil; Salmonella; T cell.

Figure 1. Overview of the immune response to Salmonella infection

Salmonella bacteria enter via the intestine and use the T3SS/SPI-1 to induce uptake by the specialized M cells of the gut. Following translocation into the Peyer’s patches, Salmonella are engulfed by phagocytic cells such as macrophages, neutrophils monocytes, and DCs. Bacterial antigens are transported by DCs to the gut-draining MLNs where Salmonella-specific T cells are activated and traffic back to the intestine. These IFN-γ producing Th1 cells further activate macrophages while IL-17 producing Th17 cells recruit large numbers of neutrophils to combat infection. Salmonella use the T3SS/SPI-2 to inject effector proteins from within the SCV to modulate the immune response, such as preventing DC migration to lymph nodes. Th1 cells in the MLNs and spleen continue to activate antimicrobial macrophages to combat systemic infection in these organs. The liver is also colonized with bacteria and while it is possible that Th1 cells are important here, far less is known about the liver immune response to Salmonella infection; however, it is known that the liver tends towards an immunosuppressive, tolerant phenotype. Salmonella also infects the gallbladder where bacteria are known to persist as biofilms attached to gallstones. Almost nothing is known about the anti-Salmonella response in the gallbladder. Abbreviations: T3SS, type three secretion system; SPI, Salmonella pathogenicity island; DC, dendritic cell; MLN, mesenteric lymph node; Th, T helper; IFN, interferon; IL, interleukin; SCV, Salmonella containing vacuole.