Lysophospholipid sensing triggers secretion of flagellin from pathogenic salmonella.
Flagellin induces inflammatory and innate immune responses through activation of Toll-like receptor 5. Here we show that proinflammatory monomeric flagellin produced by salmonella during infection of intestinal epithelial cells was not derived from polymeric bacterial cell wall-associated flagellum but instead was synthesized and secreted de novo by the bacterium after direct sensing of host-produced lysophospholipids. Inhibition of lysophospholipid biosynthesis in intestinal epithelial cells reduced flagellin production and release from salmonella. Lysophospholipids induced a cAMP-dependent signaling pathway in salmonella that resulted in production and secretion of active flagellin. The induction of Toll-like receptor ligand synthesis and secretion by a host signal represents a previously unknown regulatory mechanism for inflammation and innate immunity during infection with a bacterial pathogen.
Subramanian
Naeha
N
Hybridoma Laboratory, National Institute of Immunology, New Delhi 110 067, India.
Qadri
Ayub
A
D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D005408:Flagellin / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology / Q000382:microbiology; D012475:Salmonella / Q000378:metabolism / Q000472:pathogenicity*; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D051198:Toll-Like Receptor 5 / Q000235:genetics / Q000502:physiology*
D051198:Toll-Like Receptor 5; D005408:Flagellin; D000242:Cyclic AMP