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Thrombocytopenia Impairs Host Defense Against Burkholderia pseudomallei (Melioidosis)
Emma Birnie1, Theodora A M Claushuis1, Gavin C K W Koh2
1Center for Experimental and Molecular Medicine, Amsterdam University Medical Center (UMC), University of Amsterdam, The Netherlands.
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.
Insights
Low platelet counts (thrombocytopenia) predict mortality in melioidosis patients. In experimental models, platelets are crucial for host defense against Burkholderia pseudomallei, protecting against mortality and maintaining vascular integrity.
Area of Science:
- Infectious Diseases
- Hematology
- Immunology
Background:
- Melioidosis, caused by Burkholderia pseudomallei, is a significant cause of pneumosepsis in Southeast Asia with high mortality (up to 40%).
- The role of platelets in the host response to B. pseudomallei infection remains incompletely understood.
Purpose of the Study:
- To investigate the association between platelet counts and mortality in patients with melioidosis.
- To elucidate the functional role of platelets in experimental B. pseudomallei infection.
Main Methods:
- Retrospective analysis of 1160 patients with culture-proven melioidosis to correlate platelet counts with mortality.
- Murine models using platelet-depleting antibodies and glycoprotein Ibα-deficient mice to assess the impact of platelet reduction on B. pseudomallei infection outcomes.
Main Results:
- Thrombocytopenia at admission was observed in 31% of patients and independently predicted mortality.
- Platelet depletion in mice led to increased mortality, higher bacterial loads, impaired vascular integrity with lung bleeding, and reduced neutrophil influx.
- Glycoprotein Ibα-deficient mice exhibited reduced platelet counts and compromised local lung defense during infection.
Conclusions:
- Thrombocytopenia is a significant predictor of mortality in melioidosis.
- Platelets play a critical protective role in host defense against B. pseudomallei by enhancing innate immunity and preserving vascular integrity.
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