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A two-step activation mechanism enables mast cells to differentiate their response between extracellular and invasive enterobacterial infection. | LitMetric

AI Article Synopsis

  • Mast cells are key players in the immune system, located in mucosal tissues, and help defend against infections, particularly from bacteria like Salmonella Typhimurium (S.Tm).
  • The study reveals that mast cells can differentiate between extracellular bacteria and those that invade host cells, adjusting their cytokine secretion in response to the type of infection.
  • Invasive S.Tm leads to a strong inflammatory response in mast cells through a two-step activation process involving the recognition of bacterial factors and cellular signaling pathways, which also enhances the survival and maturation of macrophages.

Article Abstract

Mast cells localize to mucosal tissues and contribute to innate immune defense against infection. How mast cells sense, differentiate between, and respond to bacterial pathogens remains a topic of ongoing debate. Using the prototype enteropathogen Salmonella Typhimurium (S.Tm) and other related enterobacteria, here we show that mast cells can regulate their cytokine secretion response to distinguish between extracellular and invasive bacterial infection. Tissue-invasive S.Tm and mast cells colocalize in the mouse gut during acute Salmonella infection. Toll-like Receptor 4 (TLR4) sensing of extracellular S.Tm, or pure lipopolysaccharide, causes a modest induction of cytokine transcripts and proteins, including IL-6, IL-13, and TNF. By contrast, type-III-secretion-system-1 (TTSS-1)-dependent S.Tm invasion of both mouse and human mast cells triggers rapid and potent inflammatory gene expression and >100-fold elevated cytokine secretion. The S.Tm TTSS-1 effectors SopB, SopE, and SopE2 here elicit a second activation signal, including Akt phosphorylation downstream of effector translocation, which combines with TLR activation to drive the full-blown mast cell response. Supernatants from S.Tm-infected mast cells boost macrophage survival and maturation from bone-marrow progenitors. Taken together, this study shows that mast cells can differentiate between extracellular and host-cell invasive enterobacteria via a two-step activation mechanism and tune their inflammatory output accordingly.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10828507PMC
http://dx.doi.org/10.1038/s41467-024-45057-wDOI Listing

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