Salmonella AvrA modulates innate immune signaling in a mammalian model of enteric infection

The enteric pathogen Salmonella typhimurium secretes preformed effector proteins into host cells via a type III secretion system (TTSS). These effector proteins modulate host cells’ responses to facilitate the bacterial lifecycle. Our laboratory has previously reported that the Salmonella effector AvrA, when transfected into epithelial cells in vitro, inhibited the NF‐kappaB proinflammatory signaling pathway and induced apoptosis. In order to study how AvrA functions in a living mammalian host, we tested wild type Salmonella typhimurium (SL3201) and Salmonella bearing an inactive AvrA gene in a mouse model as well as in an epithelial cell line. We found that by 6 to 12h post oral infection, there was more neutrophil infiltration into ceca of mice infected with AvrA null Salmonella, seen histologically and quantified by myeloperoxidase (MPO) activity (about 2.5 fold higher). The AvrA null Salmonella also induced a more rapid and intense systemic inflammatory response, showing elevated serum KC (keratinocyte‐derived chemokine‐murine homolog of IL‐8) (2.6 fold higher, P<0.01). In vitro, the AvrA null Salmonella induced less apoptosis than the parent strain. We conclude that AvrA serves to repress innate immune signaling during the initial contact between the pathogen and the epithelia. This research was supported by NIH AI64462