title: The role of platelet MyD88 in host response during gram-negative sepsis.
abstract: BACKGROUND
  Beside their role in hemostasis, platelets serve as sentinel cells in host defense during infection. In sepsis, platelets have been implicated in both beneficial (antibacterial) and detrimental responses (thrombosis and organ damage). Toll-like receptors and their common adaptor, myeloid differentiation factor 88 (MyD88), are essential for pathogen recognition and protective immunity. Platelets express functional Toll-like receptors and MyD88, which participate in platelet responsiveness to bacterial agonists.
  
  
  OBJECTIVE
  Considering the pivotal involvement of platelets and MyD88 in the host response to bacteria, we studied the role of platelet MyD88 in gram-negative sepsis using intravenous and airway infections with the common human sepsis pathogen Klebsiella pneumoniae.
  
  
  METHODS
  Platelet-specific Myd88(-/-) mice were generated by crossing mice with a conditional Myd88 flox allele with mice expressing Cre recombinase controlled by the platelet factor 4 promoter. In a reverse approach, full Myd88(-/-) mice were transfused with wild-type platelets.
  
  
  RESULTS
  In both settings, platelet MyD88 did not impact on bacterial growth or dissemination. In addition, platelet MyD88 did not influence hallmark sepsis responses such as thrombocytopenia, coagulation or endothelial activation, or distant organ injury. Platelet MyD88 played no role in lung pathology during pneumonia-derived sepsis.
  
  
  CONCLUSIONS
  Despite known literature, platelet MyD88-dependent TLR signaling does not contribute to the host response during gram-negative sepsis.
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: S F
authors.initials: SF
authors.lastname: de Stoppelaar
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: T A M
authors.initials: TA
authors.lastname: Claushuis
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: M P B
authors.initials: MP
authors.lastname: Jansen
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chaoyang District, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Hou
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: J J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: van 't Veer
authors.affiliation: Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Experimental and Molecular Medicine (CEMM), Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000150:complications / Q000276:immunology / Q000382:microbiology; D058491:Bacterial Load; D001777:Blood Coagulation; D001792:Blood Platelets / Q000276:immunology*; D018932:Chemokine CCL2 / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology; D065206:Extracellular Traps; D005260:Female; D007710:Klebsiella Infections / Q000097:blood / Q000276:immunology* / Q000628:therapy; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000502:physiology*; D017713:Platelet Transfusion; D018410:Pneumonia, Bacterial / Q000097:blood / Q000150:complications / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018805:Sepsis / Q000097:blood / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D016037:Single-Blind Method; D013154:Spleen / Q000473:pathology; D051193:Toll-Like Receptors / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha
keywords: Toll-like receptors; mice; myeloid differentiation factor 88; platelets; pneumonia; sepsis