Salmonella activation of STAT3 signaling by SarA effector promotes intracellular replication and production of IL-10

Salmonella enterica is an important foodborne pathogen that utilizes secreted effector proteins to manipulate host pathways to facilitate survival and dissemination. Different S. enterica serovars cause disease syndromes ranging from self-limited gastroenteritis to typhoid fever and vary in their repertoire of effectors. We leveraged this natural diversity to identify stm2585, here designated sarA (Salmonella anti-inflammatory response activator), as a Salmonella effector secreted primary by the SPI-2 type III secretion system. SarA is necessary and sufficient to induce STAT3 phosphorylation and IL-10 production, contributing to intracellular replication in vitro and bacterial load at systemic sites in mice. These results demonstrate that Salmonella has evolved effector mechanisms for regulating a host anti-inflammatory signaling pathway important in infection, autoimmunity, and cancer. Two human LCLs' mRNA profiles from WT, Salmonella Typhimurium and ΔsarA S. Typhimurium mutant infections were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500 platform.