| Autor: |
Jaslow, Sarah L., Gibbs, Kyle D., Fricke, W. Florian, Wang, Liuyang, Pittman, Kelly J., Mammel, Mark K., Thaden, Joshua T., Fowler, Vance G., Hammer, Gianna E., Elfenbein, Johanna R., Ko, Dennis C. |
| Zdroj: |
Cell Reports; June 2018, Vol. 23 Issue: 12 p3525-3536, 12p |
| Abstrakt: |
Salmonella entericais an important foodborne pathogen that uses secreted effector proteins to manipulate host pathways to facilitate survival and dissemination. Different S. entericaserovars cause disease syndromes ranging from gastroenteritis to typhoid fever and vary in their effector repertoire. We leveraged this natural diversity to identify stm2585, here designated sarA(Salmonella anti-inflammatory response activator), as a Salmonellaeffector that induces production of the anti-inflammatory cytokine IL-10. RNA-seq of cells infected with either ΔsarAor wild-type S.Typhimurium revealed that SarA activates STAT3 transcriptional targets. Consistent with this, SarA is necessary and sufficient for STAT3 phosphorylation, STAT3 inhibition blocks IL-10 production, and SarA and STAT3 interact by co-immunoprecipitation. These effects of SarA contribute to intracellular replication in vitroand bacterial load at systemic sites in mice. Our results demonstrate the power of using comparative genomics for identifying effectors and that Salmonellahas evolved mechanisms for activating an important anti-inflammatory pathway. |
| Databáze: |
Supplemental Index |
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