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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Published in:Journal of thrombosis and haemostasis Vol. 13; no. 9; pp. 1709 - 1720
Main Authors: Stoppelaar, S. F., Claushuis, T. A. M., Jansen, M. P. B., Hou, B., Roelofs, J. J. T. H., Veer, C., Poll, T.
Format: Journal Article
Language:English
Published: England Elsevier Limited 01.09.2015
Subjects:
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
Online Access:Get full text
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Summary: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.
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ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/jth.13048