IL-18 Signaling Is Essential for Causing Streptococcal Toxic Shock-like Syndrome (STSLS)

Streptococcus suis (S. suis) is an emerging zoonotic pathogen that can cause multiple diseases, including streptococcal toxic shock-like syndrome (STSLS). The S. suis SC-19 strain could cause NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome hyperactivation, then induce a cytokine storm and STSLS. Although IL-18 is the downstream effector of NLRP3 signaling, the role of IL-18 signaling on STSLS remains to be elucidated. Thus, il18r1 gene knockout mice were constructed and challenged with the SC-19 strain. Alleviated clinical signs and tissue damages, as well as improved survival were observed in il18r-/- mice compared with the WT mice post-SC-19 challenge. Meanwhile, an obvious decrease in the inflammatory cytokine levels in blood was observed in the il18r-/- mice infected with SC-19. Therefore, IL-18, the downstream effector of NLRP3 inflammasome activation, was responsible for the cytokine storm and STSLS development caused by S. suis, suggesting that IL-18/IL-18Rα signaling could serve as a new target for STSLS.