title: Involvement of the platelet-activating factor receptor in host defense against Streptococcus pneumoniae during postinfluenza pneumonia.
abstract: Although influenza infection alone may lead to pneumonia, secondary bacterial infections are a much more common cause of pneumonia. Streptococcus pneumoniae is the most frequently isolated causative pathogen during postinfluenza pneumonia. Considering that S. pneumoniae utilizes the platelet-activating factor receptor (PAFR) to invade the respiratory epithelium and that the PAFR is upregulated during viral infection, we here used PAFR gene-deficient (PAFR-/-) mice to determine the role of this receptor during postinfluenza pneumococcal pneumonia. Viral clearance was similar in wild-type and PAFR-/- mice, and influenza virus was completely removed from the lungs at the time mice were inoculated with S. pneumoniae (day 14 after influenza infection). PAFR-/- mice displayed a significantly reduced bacterial outgrowth in their lungs, a diminished dissemination of the infection, and a prolonged survival. Pulmonary levels of IL-10 and KC were significantly lower in PAFR-/- mice, whereas IL-6 and TNF-alpha were only trendwise lower. These data indicate that the pneumococcus uses the PAFR leading to severe pneumonia in a host previously exposed to influenza A.
authors.affiliation: Laboratory of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. kvandersluijs@amc.uva.nl
authors.forename: Koenraad F
authors.initials: KF
authors.lastname: van der Sluijs
authors.forename: Leontine J R
authors.initials: LJ
authors.lastname: van Elden
authors.forename: Monique
authors.initials: M
authors.lastname: Nijhuis
authors.forename: Rob
authors.initials: R
authors.lastname: Schuurman
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishii
authors.forename: Henk M
authors.initials: HM
authors.lastname: Jansen
authors.forename: René
authors.initials: R
authors.lastname: Lutter
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007109:Immunity; D009980:Influenza A virus; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000150:complications*; D009994:Osmolar Concentration; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011014:Pneumonia / Q000209:etiology* / Q000276:immunology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000254:growth & development / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D018925:Chemokines; D016207:Cytokines; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor