title: Signalling or binding: the role of the platelet-activating factor receptor in invasive pneumococcal disease.
abstract: Streptococcus pneumoniae (the pneumococcus) is an opportunistic human pathogen, which causes serious invasive disease such as pneumonia, bacteraemia and meningitis. The interaction of the bacteria with host receptors precedes the development of invasive disease. One host receptor implicated in pneumococcal adhesion to, invasion of and ultimately translocation of cell layers is the platelet-activating factor receptor (PAFR). PAFR is a G-protein coupled receptor which binds PAF, a potent phospholipid activator involved in many leucocyte functions, platelet aggregation and inflammation. PAFR has been proposed to bind S. pneumoniae and as such facilitate adhesion to, uptake by and transcytosis of endothelial cells leading to invasive disease. However, there is a shortage of biochemical data supporting direct interaction between PAFR and the bacteria, in addition to conflicting data on its role in development of invasive pneumococcal disease (IPD). In this review, we will discuss current literature on PAFR and S. pneumoniae and other pathogens,including data concerning human PAFR genetic variation related to IPD clinical aspects, to shed light on the importance of PAFR in IPD. Clarification of the role of this receptor in IPD development has the potential to enable the development of novel therapeutic strategies for treating pneumococcal disease by interfering with the PAFR.
authors: Department of Medical Microbiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Federico
authors: F
authors: Iovino
authors: Matthijs C
authors: MC
authors: Brouwer
authors: Diederik
authors: D
authors: van de Beek
authors: Grietje
authors: G
authors: Molema
authors: Jetta J E
authors: JJ
authors: Bijlsma
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D004195:Disease Models, Animal; D014644:Genetic Variation / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000502:physiology; D006801:Humans; D051379:Mice; D010980:Platelet Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D011008:Pneumococcal Infections / Q000503:physiopathology*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity / Q000502:physiology
chemical_list: D002352:Carrier Proteins; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor