The IL-17A/Neutrophil axis play a critical role in lethal infection induced by an emerging ultra-virulent <i>Streptococcus suis</i> serotype 5 strain

Streptococcus suis (S. suis) is an important emerging zoonotic pathogen. In recent years, ultra-virulent serotype 5 clinical strains have emerged in China, characterized by causing high mortality in mice at early infection, even at low inoculation doses. In this study, we investigated the characteristics of lethal infection induced by the ultra-virulent S. suis serotype 5 strain SC2022MYS167 isolated from a patient with Streptococcal toxic shock-like syndrome (STSLS) and severe pneumonia. The lethal infection was associated with excessive bacterial loads and pro-inflammatory cytokines in peripheral blood and organs. Blocking IL-17A activity effectively reduced mouse mortality at infection stages 1 and 2. The lung tissues exhibited significantly higher levels of pro-inflammatory cytokines compared to liver and spleen tissues, with elevated IL-17A levels observed exclusively in the lung tissues of moribund mice at infection stage 1. CD11b+ Ly6G+ neutrophils recruited from peripheral blood significantly colocalized with IL-17A within lung tissues. Post-infection depletion of neutrophils rescued mice from lethal infection by significantly reducing the bacterial burden and levels of IL-17A, IL-6, and TNF-α in peripheral blood. A dose-dependent relationship was observed between neutrophil-depleting antibody and protection from lethal infection. These findings indicate the critical role of the IL-17A – neutrophil axis in STSLS development, pulmonary inflammation, pathological lesions, and subsequent acute host death induced by ultra-virulent serotype 5 strains, thereby providing a promising therapeutic target for reducing patient mortality.