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

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 infection of the lung. The aim of the present study was to determine the role of caspase-11 in host defense during -evoked pneumonia and sepsis. Therefore, we infected wild-type and caspase-11-deficient () mice with a low-dose via the airways to induce a gradually evolving pneumosepsis. 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 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 mice after infection. Strikingly, analysis of cross-linked fibrin and D-dimer (markers for coagulation) revealed significantly less fibrin formation in the lungs of mice at either time point after infection. These data reveal that caspase-11 contributes to protective immunity against possibly by activation of blood coagulation in the lung.