Lysophospholipid sensing triggers secretion of flagellin from pathogenic salmonella

Nat. Immunol. 7, 583-589 (2006)

Speaker：李羽涵                          Time：2006/09/20 13:00-14:00

Commentator：鄧景浩 老師                 Place：Room 601

Abstract：

Flagellin, a principal component of bacterial flagella, is a virulence factor recognized by the Toll-like receptor 5 (TLR5). The capacity to generate inflammatory response via TLR5 is associated with monomeric flagellin, as polymers of flagellin (flagella) do not bind to TLR5¹. However, the flagellated bacteria physiologically deliver monomeric flagellin is yet not known. In this study, the authors used the intestinal epithelial cells (IECs) and cultured supernatants pre-incubated with Salmonella typhi. They found S. typhi might secret biologically active flagellin after contact with an IEC-derived stimulus. Furthermore, they identified that the secretion of monomeric flagellin was induced by host-producedlysophospholipids. After analyzing the promoter activity of flagellin and involvement of cyclic AMP (cAMP) by using an adenylate cyclase-mutant strain of S. typhimurium (Δcya-27), they found that the secretion of flagellin occurred via cAMP-dependent signaling, not flagellar shearing. After that, they co-incubated S. typhimurium with intestinal cells ex vivo or in an ileal loop model in vivo to demonstrate that release of flagellin from salmonella induced by host-derived lysophospholipids also occurred during in vivo infection. Taken together, these findings suggest that during infection of the gut with salmonella, sensing of host lysophospholipids serves as a key signal for activating release of flagellinfrom this pathogen, a new mode of regulation of inflammatory and innate immune response.

References：

1.      Smith, K.D. et al. 2003. Toll-like receptor 5 recognizes a conserved site on flagellin required for protofilament formation and bacterial motility. Nat. Immunol. 4, 1247-1255

2.      Subramanian, N. and Qadri, A. 2006. Lysophopholipid sensing triggers secretion of flagellin from pathogenic salmonella. Nat. Immunol. 7, 583-589