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Thrombocytopenia Impairs Host Defense Against Burkholderia pseudomallei (Melioidosis).

Birnie, Emma; Claushuis, Theodora A M; Koh, Gavin C K W; Limmathurotsakul, Direk; Day, Nicholas P J; Roelofs, Joris J T H; Ware, Jerry; Hou, Baidong; de Vos, Alex F; van der Poll, Tom; van 't Veer, Cornelis; Wiersinga, W Joost.
J Infect Dis; 2018 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-30312422

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.
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