Deletion of the sodA Gene Impaired the Pathogenicity of Streptococcus suis Serotype 2 to Mice by Inhibiting Caspase-1/GSDMD Pathway Activation in Macrophages

<i>Streptococcus suis</i> serotype 2 (SS2) is a major zoonotic pathogen causing infectious disease in various species, whose pathogenesis is still not well understood. The <i>sodA</i> gene is an important virulence gene of SS2 involved in the host's immune response against pathogens. This study aimed to explore the impact of <i>superoxide dismutase A</i> (<i>sodA</i>) gene deletion on the pathogenicity of SS2 to mice. In this study, mice were grouped as control, WT, and Δ<i>sodA</i>, which were intraperitoneally injected with PBS, wild-type strain HA9801, and Δ<i>sodA</i> strain, respectively. WT proved to be a more virulent strain to mice with higher bacterial loads and survival rates in mice than those for Δ<i>sodA</i>. Moreover, more-severe tissue damage was observed in the lungs, liver, spleen, and kidneys of mice injected with WT than with Δ<i>sodA</i>. Additionally, macrophages accumulate to defend against SS2, and the results indicated that <i>sodA</i> gene deficiency decreased macrophage recruitment. In in vitro studies, caspase-1 and gasdermin D (GSDMD) were activated in macrophages induced by SS2; however, the absence of the <i>sodA</i> gene significantly inhibited the expression of pro-caspase-1, caspase-1, and GSDMD-N. Moreover, deletion of the <i>sodA</i> gene also decreased Interleukin-1 beta (IL-1β) and Interleukin-18 (IL-18) release in macrophages induced by SS2. Taken together, the absence of the <i>sodA</i> gene alleviated the pathogenicity of SS2 as a result of decreased macrophage accumulation and breakage of the caspase-1/GSDMD pathway in macrophages.