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

Caspase-11 contributes to pulmonary host defense against Klebsiella pneumoniae and local activation of coagulation. Am J Physiol Lung Cell Mol Physiol. 2020 May 13;: Authors: Perlee D, De Beer R, Florquin S, van der Poll T, van 't Veer C, De Vos AF Abstract 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 hours and 48 hours after inoculation. Analysis of pulmonary IL-1a, IL-1b and TNF levels showed reduced IL-1a levels in bronchoalveolar lavage fluid and increased TNF levels in the lung of Casp11-/- mice at 48 hours after inoculation. Lung gH2AX staining (marker for cell death), lung pathology and neutrophil influx in the lung, as well as bacteri...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research