Magnolol attenuates macrophage pyroptosis triggered by Streptococcus equi subsp. zooepidemicus.

Streptococcus equi subsp. zooepidemicus (SEZ) is a zoonotic bacterial pathogen that causes life-threatening infections and various diseases such as meningitis, endocarditis and pneumonia. With the use of antibiotics being severely restricted in the international community, an alternative to antibiotics is urgently needed against bacterial. In the present study, the herbal extract magnolol protected mice against SEZ infection, reflected by increased survival rate and reduced bacterial burden. A pro-inflammatory form of cell death occurred in SEZ-infected macrophage. Magnolol downregulated the expression of pyroptosis-related proteins and reduced the formation of cell membrane pores in infected macrophages to suppress the development of subsequent inflammation. We further demonstrated that magnolol directly suppressed SEZ-induced macrophage pyroptosis, which partially protected macrophages from SEZ infection. Our study revealed that magnolol suppressed inflammation and protected mice against SEZ infection, providing a possible treatment for SEZ infection.

Gasdermin D protects against Streptococcus equi subsp. zooepidemicus infection through macrophage pyroptosis.

Streptococcus equi subsp. zooepidemicus (S. zooepidemicus, SEZ) is an essential zoonotic bacterial pathogen that can cause various inflammation, such as meningitis, endocarditis, and pneumonia. Gasdermin D (GSDMD) is involved in cytokine release and cell death, indicating an important role in controlling the microbial infection. This study investigated the protective role of GSDMD in mice infected with SEZ and examined the role of GSDMD in peritoneal macrophages in the infection. GSDMD-deficient mice were more susceptible to intraperitoneal infection with SEZ, and the white pulp structure of the spleen was seriously damaged in GSDMD-deficient mice. Although the increased proportion of macrophages did not depend on GSDMD in both spleen and peritoneal lavage fluid (PLF), deficiency of GSDMD caused the minor release of the pro-inflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-18 (IL-18) during the infection in vivo. In vitro, SEZ infection induced more release of IL-1ß, IL-18, and lactate dehydrogenase (LDH) in wild-type macrophages than in GSDMD-deficient macrophages. Finally, we demonstrated that pore formation and pyroptosis of macrophages depended on GSDMD. Our findings highlight the host defense mechanisms of GSDMD against SEZ infection, providing a potential therapeutic target in SEZ infection.