Critical roles of NLRP3 inflarnrnasome in IL-1β secretion induced by Corynebacterium pseudotuberculosis in vitro

Corynebacterium pseudotuberculosis is a prominent human and animal pathogen causing chronic inflammatory diseases. Interleukin-1 beta (IL-1 beta) is involved in the response to such pathogenic infections. However, the mechanism by which IL-1 beta is secreted during C. pseudotuberculosis infection remains unclear. This study aimed to investigate the mechanism underlying IL-1 beta secretion by macrophages infected with C. pseudotuberculosis. Herein, we firstly revealed that nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC) and caspase-1 (Casp1) play critical roles in IL-1 beta secretion rather than IL-1 beta precursor (pro-IL-1 beta) expression in C. pseudotuberculosis-infected macrophages. Toll like receptor 4 (TLR4) is partially involved in IL-1 beta secretion, while absent in melanoma 2 (AIM2) is not involved in IL-1 beta secretion by C. pseudotuberculosis-infected macrophages. In addition, nuclear factor kappa B (NF-kappa B) and p38 mitogen-activated protein kinases (p38 MAPK) inhibitors almost attenuated IL-1 beta secretion, implying that NF-kappa B and p38MAPK pathway are involved in IL-1 beta secretion in C. pseudotuberculosis-infected macrophages. Furthermore, C. pseudotuberculosis were significantly more numerous in Nlrp3(-/-), Asc(-/-), and Casp-1(-/-) macrophages than in WT macrophages at 24 h after infection (P < 0.05), indicating that NLRP3 inflammasome components limit C. pseudotuberculosis replication in macrophages. Together, these data provide novel insights into the mechanisms underlying IL-1 beta secretion in C. pseudotuberculosis-infected macrophages and further the current understanding of the host pro-inflammatory immune response against this pathogen.