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The role of platelet MyD88 in host response during gram-negative sepsis.
J Thromb Haemost 2015; 13(9):1709-20JT

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.

CONCLUSION

Despite known literature, platelet MyD88-dependent TLR signaling does not contribute to the host response during gram-negative sepsis.

Authors+Show Affiliations

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.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.Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.Key Laboratory of Infection and Immunity, Institute of Biophysics, Chaoyang District, Beijing, China.Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.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.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.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26178922

Citation

de Stoppelaar, S F., et al. "The Role of Platelet MyD88 in Host Response During Gram-negative Sepsis." Journal of Thrombosis and Haemostasis : JTH, vol. 13, no. 9, 2015, pp. 1709-20.
de Stoppelaar SF, Claushuis TA, Jansen MP, et al. The role of platelet MyD88 in host response during gram-negative sepsis. J Thromb Haemost. 2015;13(9):1709-20.
de Stoppelaar, S. F., Claushuis, T. A., Jansen, M. P., Hou, B., Roelofs, J. J., van 't Veer, C., & van der Poll, T. (2015). The role of platelet MyD88 in host response during gram-negative sepsis. Journal of Thrombosis and Haemostasis : JTH, 13(9), pp. 1709-20. doi:10.1111/jth.13048.
de Stoppelaar SF, et al. The Role of Platelet MyD88 in Host Response During Gram-negative Sepsis. J Thromb Haemost. 2015;13(9):1709-20. PubMed PMID: 26178922.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of platelet MyD88 in host response during gram-negative sepsis. AU - de Stoppelaar,S F, AU - Claushuis,T A M, AU - Jansen,M P B, AU - Hou,B, AU - Roelofs,J J T H, AU - van 't Veer,C, AU - van der Poll,T, Y1 - 2015/08/06/ PY - 2015/04/08/received PY - 2015/06/30/accepted PY - 2015/7/17/entrez PY - 2015/7/17/pubmed PY - 2016/7/7/medline KW - Toll-like receptors KW - mice KW - myeloid differentiation factor 88 KW - platelets KW - pneumonia KW - sepsis SP - 1709 EP - 20 JF - Journal of thrombosis and haemostasis : JTH JO - J. Thromb. Haemost. VL - 13 IS - 9 N2 - 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. SN - 1538-7836 UR - https://www.unboundmedicine.com/medline/citation/26178922/The_role_of_platelet_MyD88_in_host_response_during_gram_negative_sepsis_ L2 - https://doi.org/10.1111/jth.13048 DB - PRIME DP - Unbound Medicine ER -