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

S Fillon, K Soulis, S Rajasekaran… - The Journal of …, 2006 - journals.aai.org
S Fillon, K Soulis, S Rajasekaran, H Benedict-Hamilton, JN Radin, CJ Orihuela, KC El Kasmi
The Journal of Immunology, 2006journals.aai.org
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 …
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.
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