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Streptococcus equi ssp. zooepidemicus (SEZ) predominantly acts as a zoonotic pathogen, capable of infecting a diverse range of animal species including human. Gasdermin D (GSDMD) exhibited comprehensive functions in host against different pathogenic microorganism. This study aimed to investigate the role of GSDMD in host against SEZ. Mice were administrated with SEZ via intranasal intubation for 24 h (3 × 10 6 CFU), GSDMD protein expression significantly increased in the lung tissue of mice infected with SEZ. For further research on the role of GSDMD during SEZ infection, GSDMD -/- mice and WT mice were treated with SEZ via intranasal intubation for 24 h (3 × 10 6 CFU). GSDMD -/- mice showed less severe lung tissue due to fewer bacteria colonization. Numerous neutrophils were recruited into lung tissues in GSDMD -/- mice, related to the release of CXCL1 and CXCL2 regulated by p65 phosphorylation. In further study, neutrophils of WT and GSDMD -/- mice were isolated and treated with SEZ (multiplicity of infection, MOI = 10, 4 h). The absence of GSDMD alleviated the death of neutrophils, in addition, GSDMD deficiency could promote translocation of p65 from the cytoplasm into the nucleus in neutrophil, which may contribute to the release of IL-1β and TNF-α. This study demonstrated a novel function of GSDMD in host immune response to SEZ invading, indicating that GSDMD deficiency ameliorated SEZ infection through enhancing neutrophil accumulation into infected site, and activating NF-κB pathway in neutrophil to release cytokines against SEZ. Our study suggested that inhibition of host GSDMD may be an effective method against SEZ., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Streptococcus equi ssp. zooepidemicus (S. zooepidemicus, SEZ) is a zoonotic bacterial pathogen that can cause various inflammation, including pneumonia. As the most abundant leukocytes in the circulation, neutrophils are the first wave of leukocytes to arrive in the lung upon infection. This study aims to evaluate the effect of caspase-1 on the host response to SEZ infection in a mouse model. Intranasal exposure to SEZ induced the expression of caspase-1 in wild-type mice lung, and increased the number of neutrophils in the alveolar cavity and alveolar wall. In addition, caspase-1 deficiency reduced the transcription levels of IL-1α, IL-1β, IL-6, and TNF-α in the lungs of infected mice, which was accompanied by decreased recruitment of pulmonary neutrophils. Moreover, knocking out caspase-1 decreased the bactericidal activity of neutrophils and promoted the pulmonary bacterial load. In line with this, the mortality of caspase-1 -/- mice infected with SEZ was significantly increased compared with those of caspase-1 +/+ mice. Collectively, recruiting neutrophils and enhancing the bactericidal ability of neutrophils are important means for caspase-1 to promote bacterial clearance., (Copyright © 2022 Elsevier B.V. All rights reserved.)