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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.