Caspase-11 and NLRP3 exacerbate systemic Klebsiella infection through reducing mitochondrial ROS production

These results suggest that caspase-11 and NLRP3 contribute to K. pneumoniae-induced sepsis by impairing mitochondrial function and reducing ROS production in macrophages, thereby compromising bacterial clearance. The observed reduction in lung injury and increased survival in caspase-11- and NLRP3-deficient mice indicate that targeting these pathways may offer potential therapeutic strategies to improve host defense against systemic K. pneumoniae infection.

Our findings demonstrate that K. pneumoniae systemic infection results in severe lung injury and significant bacterial accumulation in multiple organs, with the highest burden in the lungs. Deficiency of caspase-11 or NLRP3 led to prolonged survival, a reduction in pulmonary bacterial load, increased blood oxygen levels, and decreased IL-6 levels in the lungs compared to WT controls. Furthermore, caspase-11- and NLRP3-deficient macrophages exhibited elevated mitochondrial ROS production in response to K. pneumoniae, which correlated with more effective bacterial clearance.