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

Sophie Fillon, Konstantinos Soulis, Surender Rajasekaran, Heather Benedict-Hamilton, Jana N. Radin, Carlos J. Orihuela, Karim C. El Kasmi, Gopal Murti, Deepak Kaushal, M. Waleed Gaber, Joerg R. Weber, Peter J. Murray, Elaine I. Tuomanen

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)6182-6191
Number of pages10
JournalJournal of Immunology
Volume177
Issue number9
DOIs
StatePublished - Nov 1 2006

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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