NLRP3/ASC/Caspase-l axis and serine protease activity are involved in neutrophil IL-1beta processing during Streptococcus pneumoniae infection

摘要

Streptococcus pneumoniae is a pathogenic bacterium that can cause severe invasive diseases, such as pneumonia, otitis media and meningitis. The pro-inflammatory cytokine, IL-1 beta, has been reported to play important role in host defense against S. pneumoniae. The mechanism of IL-1 beta maturation and secretion in macrophages has been well studied. However, the precise mechanism of IL-1 beta processing within neutrophils upon S. pneumoniae infection remains unclear. In this study, mouse peritoneal neutrophils from C57BL/6 WT and inflammasome components knockout mice were infected by S. pneumoniae in vitro. The results showed that NLRP3 inflammasome is critically involved in neutrophil IL-1 beta secretion, while the AIM2 and NLRC4 inflammasomes were dispensable. Moreover, the upstream kinase, JNK, modulates ASC oligomerization and consequent caspase-1 activation and IL-1 beta secretion. Additionally, neutrophil serine proteases also participate in IL-1 beta secretion by mediating ASC oligomerization and caspase-1 activation. Taken together, these findings indicated that both the NLRP3 inflammasome-related pathway and neutrophil serine protease mediate IL-1 beta processing upon S. pneumoniae infection.