The role of platelet MyD88 in host response during gram‐negative sepsis

Summary 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,...

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Vydáno v:	Journal of thrombosis and haemostasis Ročník 13; číslo 9; s. 1709 - 1720
Hlavní autoři:	Stoppelaar, S. F., Claushuis, T. A. M., Jansen, M. P. B., Hou, B., Roelofs, J. J. T. H., Veer, C., Poll, T.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Elsevier Limited 01.09.2015
Témata:	Animals Bacteremia - complications Bacteremia - immunology Bacteremia - microbiology Bacterial Load Blood Coagulation Blood Platelets - immunology Chemokine CCL2 - blood Endothelium, Vascular - physiopathology Extracellular Traps Female Klebsiella Infections - blood Klebsiella Infections - immunology Klebsiella Infections - therapy Klebsiella pneumoniae - immunology Liver - pathology Lung - pathology Male Mice Mice, Inbred C57BL Mice, Knockout myeloid differentiation factor 88 Myeloid Differentiation Factor 88 - deficiency Myeloid Differentiation Factor 88 - physiology Platelet Transfusion platelets pneumonia Pneumonia, Bacterial - blood Pneumonia, Bacterial - complications Pneumonia, Bacterial - immunology Pneumonia, Bacterial - microbiology Pneumonia, Bacterial - pathology Rodents Sepsis Sepsis - blood Sepsis - etiology Sepsis - immunology Sepsis - therapy Single-Blind Method Spleen - pathology Toll-Like Receptors - blood Toll‐like receptors Tumor Necrosis Factor-alpha - analysis Toll-like receptors myeloid differentiation factor 88 pneumonia mice platelets sepsis
ISSN:	1538-7933, 1538-7836, 1538-7836
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Popis
Shrnutí:	Summary 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. Conclusion Despite known literature, platelet MyD88‐dependent TLR signaling does not contribute to the host response during gram‐negative sepsis.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1538-7933 1538-7836 1538-7836
DOI:	10.1111/jth.13048