Platelets are essential for survival of respiratory-restricted viral infection

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Abstract
Platelets are small, anucleate cells derived from megakaryocytes and are known for their essential role in hemostasis. Over the past decade, they have also emerged as important immune modulators, able to affect viral replication and leukocyte behavior. Most studies on platelets and viral infections have been focused on severe viremic infections. However, the role of platelets in respiratory-restricted infections remains unclear. We investigated the role of platelet-mediated immunity using murine respirovirus (SeV) as a model. First, in vitro experiments showed that platelets become activated in response to and internalize SeV. Next, a mouse model of platelet depletion was used to understand how platelets contribute to host defense against SeV in vivo. After intranasal (i.n.) infection, control mice with normal platelet counts had mild symptoms with few deaths. Despite no significant differences in viral load, platelet-depleted mice were highly susceptible to infection, had severe weight loss, and high mortality rates. Further analysis revealed that platelets modulate neutrophil responses in the lung. Platelet depletion increased neutrophil numbers but decreased neutrophil apoptosis, as evidenced via labeling of lungs with activated caspase 3. Additionally, we demonstrate platelets augment neutrophil apoptosis in the presence of SeV. Together, these data demonstrate that platelets are critical for host responses during respiratory viral infections through regulating neutrophil dynamics and not through controlling viral burden. This study reinforces platelets as a potential therapeutic target to combat severe pulmonary viral infection and to prevent its progression to life-threatening cases of bronchiolitis or respiratory failure.
Funding Information
  • American Heart Association and the Hablitzel Family Predoctoral Fellowship (23PRE1019987)
  • National Institutes of Health (AI155545)
  • National Institutes of Health (AI165521)

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