Now you see me, now you don't: the interaction of Salmonella with innate immune receptors

Key Points Several distinct pattern recognition receptors cooperate during Salmonella -induced bacteraemia to coordinate responses against lipopolysaccharide through canonical and non-canonical pathways. Different non-canonical pathways are important for Salmonella -induced gastroenteritis, and this differential activation of innate immune responses results from the differential expression of pattern recognition receptors in epithelial cells and mucosal phagocytes. The rapid repression of virulence genes during invasion of the intestinal mucosa enables the causative agent of typhoid fever to evade recognition by pattern recognition receptors. The virulence-associated capsular polysaccharide inhibits activation of complement, a pattern recognition receptor that cooperates with Toll-like receptors and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) to orchestrate antibacterial responses. Salmonella enterica serovars are human pathogens that are commonly used to study host–bacterium interaction mechanisms. In this Review, Bäumler and colleagues discuss how the innate immune system recognizes non-typhoidal and typhoidal serovars, and how specific virulence factors and changes in virulence gene regulation alter innate immune responses. Salmonella enterica serovars are associated with an estimated 1 million deaths annually and are also useful model organisms for investigating the mechanisms of host–bacterium interactions. The insights gained from studies on non-typhoidal Salmonella (NTS) serovars have provided a fascinating overview of the mechanisms by which the innate immune system detects and responds to bacterial pathogens. However, specific virulence factors and changes in virulence gene regulation in S. enterica subsp. enterica serovar Typhi alter the innate immune responses to this pathogen. In this Review, we compare and contrast the interactions of S. Typhi and NTS serovars with host innate immune receptors and discuss why the disease manifestations associated with S. Typhi infection differ considerably from those associated with the closely related NTS serovars.