Caspase-11 contributes to pulmonary host defense against Klebsiella pneumoniae and local activation of coagulation

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Klebsiella (K.) pneumoniae is a common cause of gram-negative pneumonia and sepsis. Caspase-11 is an intracellular receptor for lipopolysaccharide and regulates pyroptosis, a specific form of inflammatory cell death, which aids in host defense against intracellular gram-negative bacteria. Recently, caspase-11 has also been implicated in blood coagulation. Previously, we found that local fibrin formation contributes to protective immunity against Klebsiella infection of the lung. The aim of the present study was to determine the role of caspase-11 in host defense during K. pneumoniae-evoked pneumonia and sepsis. Therefore, we infected wild-type and caspase-11-deficient (Casp11-/-) mice with a low-dose K. pneumoniae via the airways to induce a gradually evolving pneumosepsis. Casp11-/- mice displayed increased bacterial numbers in the lung 12 h and 48 h after inoculation. Analysis of pulmonary IL-1α, IL-1β, and TNF levels showed reduced IL-1α levels in bronchoalveolar lavage fluid and increased TNF levels in the lung of Casp11-/- mice at 48 h after inoculation. Lung γH2AX staining (marker for cell death), lung pathology and neutrophil influx in the lung, as well as bacterial dissemination and organ damage, however, were not altered in Casp11-/- mice after Klebsiella infection. Strikingly, analysis of cross-linked fibrin and D-dimer (markers for coagulation) revealed significantly less fibrin formation in the lungs of Casp11-/- mice at either time point after Klebsiella infection. These data reveal that caspase-11 contributes to protective immunity against K. pneumoniae possibly by activation of blood coagulation in the lung.
Original languageEnglish
Pages (from-to)L105-L114
JournalAmerican journal of physiology. Lung cellular and molecular physiology
Issue number1
Publication statusPublished - 1 Jul 2020


  • Blood coagulation
  • Caspase-11
  • Inflammasome
  • Pneumonia
  • Sepsis

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