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NLRP3/ASC/Caspase-1 axis and serine protease activity are involved in neutrophil IL-1β processing during Streptococcus pneumoniae infection
- Zhang, Tingjuan, Du, Huihui, Feng, Siwei, Wu, Rui, Chen, Tingting, Jiang, Jiali, Peng, Yuanyi, Ye, Chao, Fang, Rendong
- Biochemical and biophysical research communications 2019 v.513 no.3 pp. 675-680
- Streptococcus pneumoniae, caspase-1, enzyme activity, inflammasomes, interleukin-1beta, knockout mutants, macrophages, meningitis, mice, mitogen-activated protein kinase, neutrophils, oligomerization, otitis media, pneumonia, secretion, serine proteinases
- Streptococcus pneumoniae is a pathogenic bacterium that can cause severe invasive diseases, such as pneumonia, otitis media and meningitis. The pro-inflammatory cytokine, IL-1β, has been reported to play important role in host defense against S. pneumoniae. The mechanism of IL-1β maturation and secretion in macrophages has been well studied. However, the precise mechanism of IL-1β 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-1β secretion, while the AIM2 and NLRC4 inflammasomes were dispensable. Moreover, the upstream kinase, JNK, modulates ASC oligomerization and consequent caspase-1 activation and IL-1β secretion. Additionally, neutrophil serine proteases also participate in IL-1β 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-1β processing upon S. pneumoniae infection.