Hypervirulent Klebsiella Pneumonia induces Liver Abscess by promoting Neutrophil Extracellular Trap Formation through Activating NLRP3 Inflammasome

Hypervirulent Klebsiella pneumoniae (hvKP) has spread globally since first described in the Asian Pacific Rim. Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. However, the role of hvKP pathogenicity on neutrophil extracellular trap formation remains unclear. Here we show the influence of hvKP strain NTUH-K2044 on NETosis and related mechanisms. We investigate that hvKP significantly lead to liver abscess and a large number of neutrophils infiltration in liver tissues from murine models and had hypermucoviscosity by carried rmpA gene. hvKP enhanced the protein levels of MPO and promoted the chromatin depolymerization of human peripheral blood neutrophils compared with classic Klebsiella pneumonia (cKP) strain HS11286. In addition, hvKP markedly promoted the ROS and cytokines levels in neutrophils. Moreover, hvKP significantly accelerated the activation of NLRP3 inflammatory and the production of NETosis compared with cKP in neutrophils. Therefore, hvKP has a stronger ability to resist neutrophil killing and promote the activation of NLRP3 inflammatory and induce NETosis. Our findings provide a novel mechanism underlying of hvKP innate immune evasion