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Updated: Apr 22, 2026
Characterizing Salmonella Typhimurium-induced Septic Peritonitis in Mice
Published on: July 29, 2022
Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice
Sacha F de Stoppelaar1, Cornelis van 't Veer1, Theodora A M Claushuis1
1Center for Infection and Immunity Amsterdam, Center for Experimental and Molecular Medicine.
Abstract:
Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median of 5 × 10(9)/L or to 5 to 13 × 10(9)/L by administration of a depleting antibody in mice infected with Klebsiella via the airways. Thrombocytopenia was associated with strongly impaired survival during pneumonia-derived sepsis proportional to the extent of platelet depletion. Thrombocytopenic mice demonstrated PC-dependent enhanced bacterial growth in lungs, blood, and distant organs. Severe thrombocytopenia resulted in hemorrhage at the primary site of infection, but not in distant organs. PCs of 5 to 13 × 10(9)/L were sufficient to largely maintain hemostasis in infected lungs. Thrombocytopenia did not influence lung inflammation or neutrophil recruitment and did not attenuate local or systemic activation of coagulation or the vascular endothelium. PCs <5 × 10(9)/L even resulted in enhanced coagulation and endothelial cell activation, which coincided with increased proinflammatory cytokine levels. In accordance, low PCs in whole blood enhanced Klebsiella-induced cytokine release in vitro. These data suggest that platelets play an important role in host defense to Klebsiella pneumosepsis.
Insights
Severe thrombocytopenia impairs survival in Klebsiella pneumoniae sepsis by promoting bacterial growth. Platelets are crucial for host defense, with low counts enhancing inflammation and cytokine release.
Area of Science:
- Immunology
- Microbiology
- Pathophysiology
Background:
- Thrombocytopenia (low platelet counts) is common in sepsis and linked to poor outcomes.
- Platelets' role in sepsis, particularly pneumonia-derived sepsis, requires further investigation.
Purpose of the Study:
- To investigate the role of platelets in host defense during Klebsiella pneumoniae-induced pneumonia sepsis using a mouse model.
- To determine the impact of varying degrees of thrombocytopenia on survival, bacterial dissemination, and host inflammatory responses.
Main Methods:
- A mouse model of pneumonia-derived sepsis using Klebsiella pneumoniae was established.
- Platelet counts were experimentally reduced using a depleting antibody.
- Survival rates, bacterial loads in various organs, hemorrhage, inflammation, neutrophil recruitment, coagulation, and endothelial activation were assessed.
Main Results:
- Thrombocytopenia significantly impaired survival in a platelet count-dependent manner.
- Reduced platelet counts led to enhanced bacterial growth in lungs, blood, and distant organs.
- Severe thrombocytopenia caused hemorrhage at the infection site but not distant organs.
- Platelet counts were sufficient to maintain hemostasis in infected lungs.
- Thrombocytopenia did not affect lung inflammation or neutrophil recruitment but could enhance coagulation and endothelial activation at very low counts.
- Low platelet counts amplified Klebsiella-induced cytokine release in vitro.
Conclusions:
- Platelets play a critical role in host defense against Klebsiella pneumoniae pneumonia sepsis.
- The extent of platelet depletion directly correlates with disease severity and survival.
- Platelets influence bacterial containment and modulate inflammatory and coagulation responses during sepsis.
