Nature Immunology7, 583 - 589 (2006)
Published online: 30 April 2006; | doi:10.1038/ni1336
Lysophospholipid sensing triggers secretion of flagellin from pathogenic salmonella
Naeha Subramanian
& Ayub Qadri
Hybridoma Laboratory, National Institute of Immunology, New Delhi 110 067, India.
Correspondence should be addressed to Ayub Qadri ayub@nii.res.in
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.
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