Conclusion
Nlrp3 inflammasome activation triggered by SLY in macrophages played an important role in the pathogenesis of STSS.
Methods
To verify the role of suilysin (SLY) in STSS, we infected bone-marrow-derived macrophages (BMDMs) in vitro and C57BL/6J mice intraperitoneally (IP) with the SS2 wild-type (WT) strain or isogenic sly mutant (∆SLY) to measure the interleukin (IL)-1β release and survival rate. To determine the role of inflammasome activation and pyroptosis in STSS, we infected BMDMs from WT and various deficient mice, including Nlrp3-deficient (Nlrp3-/-), Nlrc4-deficient (Nlrc4-/-), Asc-deficient (Asc-/-), Aim2-deficient (Aim2-/-), Caspase-1/11-deficient (Caspase-1/11-/-), and Gsdmd-deficient (Gsdmd-/-) ex vivo, and IP injected WT, Nlrp3-/-, Caspase-1/11-/-, and Gsdmd-/- mice with SS2, to compare the IL-1β releases and survival rate in vivo.
Objective
The aim of this study was to investigate the molecular mechanism of inflammasome activation in response to Streptococcus suis serotype 2 (SS2) infection and its contribution to the development of streptococcal toxic shock-like syndrome (STSS).
Results
The SS2-induced IL-1β production in mouse macrophages is mediated by SLY ex vivo. The survival rate of WT mice infected with SS2 was significantly lower than that of mice infected with the ∆SLY strain in vivo. Furthermore, SS2-triggered IL-1β releases, and the cytotoxicity in the BMDMs required the activation of the NOD-Like Receptors Family Pyrin Domain Containing 3 (Nlrp3), Caspase-1/11, and gasdermin D (Gsdmd) inflammasomes, but not the Nlrc4 and Aim2 inflammasomes ex vivo. The IL-1β production and survival rate of WT mice infected with SS2 were significantly lower than those of the Nlrp3-/-, Caspase-1/11-/-, and Gsdmd-/- mice in vivo. Finally, the inhibitor of the Nlrp3 inflammasome could reduce the IL-1β release and cytotoxicity of SS2-infected macrophages ex vivo and protect SS2-infected mice from death in vivo.