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<p><i>Salmonella enterica</i> subsp. <i>enterica</i> serovar Typhimurium (<i>S</i>. Typhimurium) manipulates cellular processes through the translocation of effector molecules into the host cell cytosol. Using a recently established neonatal <i>S</i>. Typhimurium infection model, we provide functional insights into how <i>Salmonella</i> outer protein B (SopB) suppresses early mucosal tissue inflammation and prolongs host survival. Mechanistically, SopB prevents a disintegrin and metalloprotease 17 (ADAM17) activation, plasma membrane translocation and the release of membrane-bound TNFα from enterocytes and reduces epithelial secretion of IL-18 via mTOR-controlled secretory autophagy. This abolishes the early epithelial transcriptional response and reduces immune cell recruitment and programmed cell death-mediated mucosal barrier disruption delaying disease progression. The immunosuppressive effect of SopB is independent of the C-terminally encoded phosphatidylinositol phosphatase and phosphotransferase activity but requires an intact N-terminal domain. Also, it is restricted to the neonatal mouse model characterised by <i>Salmonella</i> pathogenicity island (SPI)1 type 3 secretion system (T3SS)-dependent enterocyte invasion-driven mucosal translocation. Thus, here we demonstrate that SopB suppresses the early, post-transcriptional regulation of epithelial cytokine release in an inositol phosphatase-independent manner likely promoting pathogen transmission.</p>

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Salmonella SopB suppresses post-transcriptionally regulated cytokine release to reduce early tissue inflammation and delay disease progression

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月6日

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  • Nour Diab,
  • Chiun Huei Yong,
  • Eva-Lena Stange,
  • Marlène S. Birk,
  • Matthias A. Schmitz,
  • Stefan Düsterhöft,
  • Jonas Pes,
  • Kira Noemi Ferle,
  • Isabel Karkossa,
  • Kristin Schubert,
  • Jörg Deiwick,
  • Mihael Vucur,
  • Tom Luedde,
  • Natalia Torow,
  • Andreas Ludwig,
  • Aline Dupont,
  • Joel Selkrig,
  • Martin von Bergen,
  • Michael Hensel,
  • Kaiyi Zhang,
  • Mathias W. Hornef

摘要

Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) manipulates cellular processes through the translocation of effector molecules into the host cell cytosol. Using a recently established neonatal S. Typhimurium infection model, we provide functional insights into how Salmonella outer protein B (SopB) suppresses early mucosal tissue inflammation and prolongs host survival. Mechanistically, SopB prevents a disintegrin and metalloprotease 17 (ADAM17) activation, plasma membrane translocation and the release of membrane-bound TNFα from enterocytes and reduces epithelial secretion of IL-18 via mTOR-controlled secretory autophagy. This abolishes the early epithelial transcriptional response and reduces immune cell recruitment and programmed cell death-mediated mucosal barrier disruption delaying disease progression. The immunosuppressive effect of SopB is independent of the C-terminally encoded phosphatidylinositol phosphatase and phosphotransferase activity but requires an intact N-terminal domain. Also, it is restricted to the neonatal mouse model characterised by Salmonella pathogenicity island (SPI)1 type 3 secretion system (T3SS)-dependent enterocyte invasion-driven mucosal translocation. Thus, here we demonstrate that SopB suppresses the early, post-transcriptional regulation of epithelial cytokine release in an inositol phosphatase-independent manner likely promoting pathogen transmission.