Platelet-activating factor receptor and innate immunity: Uptake of gram-positive bacterial cell wall into host cells and cell-specific pathophysiology

Academic Article

Abstract

  • The current model of innate immune recognition of Gram-positive bacteria suggests that the bacterial cell wall interacts with host recognition proteins such as TLRs and Nod proteins. We describe an additional recognition system mediated by the platelet-activating factor receptor (PAFr) and directed to the pathogen-associated molecular pattern phosphorylcholine that results in the uptake of bacterial components into host cells. Intravascular choline-containing cell walls bound to endothelial cells and caused rapid lethality in wild-type, Tlr2-/-, and Nod2-/- mice but not in Pafr-/- mice. The cell wall exited the vasculature into the heart and brain, accumulating within endothelial cells, cardiomyocytes, and neurons in a PAFr-dependent way. Physiological consequences of the cell wall/PAFr interaction were cell specific, being noninflammatory in endothelial cells and neurons but causing a rapid loss of cardiomyocyte contractility that contributed to death. Thus, PAFr shepherds phosphorylcholine-containing bacterial components such as the cell wall into host cells from where the response ranges from quiescence to severe pathophysiology. Copyright © 2006 by The American Association of Immunologists, Inc.
  • Authors

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    Digital Object Identifier (doi)

    Author List

  • Fillon S; Soulis K; Rajasekaran S; Benedict-Hamilton H; Radin JN; Orihuela CJ; El Kasmi KC; Murti G; Kaushal D; Gaber MW
  • Start Page

  • 6182
  • End Page

  • 6191
  • Volume

  • 177
  • Issue

  • 9