Caspase-11 deficiency impairs neutrophil recruitment and bacterial clearance in the early stage of pulmonary Klebsiella pneumoniae infection

Abstract

Klebsiella pneumoniae (K. pneumoniae) is a gram-negative pathogen, and Klebsiella pneumonia is one of the most common nosocomial infections. Canonical NLRP3 and NLRC4 inflammasome was found involved in innate immune response against K. pneumoniae, but the role of caspase-11 in K. pneumoniae infection remains undefined. It was shown that Caspase-11 knockout blocked K. pneumoniae-induced IL-1α and IL-1β secretion and pyroptosis of bone marrow-derived macrophages (BMDMs). Furthermore, caspase-11−/− mice exhibited impaired neutrophil recruitment and bacterial clearance in the early stage of K. pneumoniae infection, accompanied by a reduction in IL-1α production. Moreover, IL-1α neutralizing antibody pretreatment was found to inhibit neutrophil recruitment and bacterial clearance of wild-type mice. Together, these data suggest that caspase-11/IL-1α pathway plays an important role in defending against K. pneumoniae by recruiting neutrophils in the early stage of infection.