Critical Roles of <i>Klebsiella pneumoniae</i> Enterobactin in NLRP3 Inflammasome Activation in Airway Epithelial Cells

Klebsiella pneumoniae is a ubiquitous Gram‐negative bacterium and a common cause of pneumonia, which leads to intense lung injury and mortality that are correlated with deregulated inflammation. Emerging evidence indicates that the NLRP3 inflammasome plays a critical part in regulating inflammatory processes in various infectious diseases. However, its role in K. pneumoniae infections remains elusive. In this study, we identified a siderophore, enterobactin (Ent), from K. pneumoniae as a key factor that induces NLRP3 activation in both the pulmonary epithelial cell line A549 and lung tissue from K. pneumoniae –infected mice. A549 epithelial cells infected with an Ent‐deficient mutant ( ΔentB ) had lower Nlrp3 , Asc , and Pro-caspase-1 gene expression, caspase‐1 activity, and IL‐18 secretion than cells infected with wild‐type K. pneumoniae . No such effect was observed with THP‐1 macrophages. Ent induced NLRP3 activation and IL‐18 production in lung tissue of mice intranasally infected by K. pneumoniae strains. Interestingly, the recruitment of immune cells and production of inflammatory cytokines and chemokines were comparable in wild‐type and ΔentB strain – infected mice. Taken together, our findings provide the first example of Ent playing a role in host inflammation control by targeting NLRP3.