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Title: Thrombocytopenia Impairs Host Defense Against Burkholderia pseudomallei (Melioidosis)
Authors: Emma Birnie
Theodora A.M. Claushuis
Gavin C.K.W. Koh
Direk Limmathurotsakul
Nicholas P.J. Day
Joris J.T.H. Roelofs
Jerry Ware
Baidong Hou
Alex F. De Vos
Tom Van Der Poll
Cornelis Van't Veer
W. Joost Wiersinga
University of Cambridge
University of Oxford
University of Arkansas for Medical Sciences
Institute of Biophysics Chinese Academy of Sciences
Mahidol University
Universiteit van Amsterdam
Amsterdam UMC - University of Amsterdam
Keywords: Medicine
Issue Date: 29-Jan-2019
Citation: Journal of Infectious Diseases. Vol.219, No.4 (2019), 648-659
Abstract: © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. Background Infection with the gram-negative bacillus Burkholderia pseudomallei (melioidosis) is an important cause of pneumosepsis in Southeast Asia and has a mortality of up to 40%. We aimed to assess the role of platelets in the host response against B. pseudomallei infection. Methods Association between platelet counts and mortality was determined in 1160 patients with culture-proven melioidosis. Mice treated with (low- or high-dose) platelet-depleting antibody were inoculated intranasally with B. pseudomallei and killed. Additional studies using functional glycoprotein Ibα-deficient mice were conducted. Results Thrombocytopenia was present in 31% of patients at admission and predicted mortality in melioidosis patients even after adjustment for confounders. In our murine-melioidosis model, platelet counts decreased, and mice treated with a platelet-depleting antibody showed enhanced mortality and higher bacterial loads compared to mice with normal platelet counts. Low platelet counts had a modest impact on early-pulmonary neutrophil influx. Reminiscent of their role in hemostasis, platelet depletion impaired vascular integrity, resulting in early lung bleeding. Glycoprotein Ibα-deficient mice had reduced platelet counts during B. pseudomallei infection together with an impaired local host defense in the lung. Conclusions Thrombocytopenia predicts mortality in melioidosis patients and, during experimental melioidosis, platelets play a protective role in both innate immunity and vascular integrity.
ISSN: 15376613
Appears in Collections:Scopus 2019

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