The role of NLRP3/caspase−/GSDMD signal axis mediated cell pyroptosis in the pathogenicity of T. asahii

Cell pyroptosis serves as a critical regulatory mechanism by which host cells respond to fungal infections. However, whether pyroptosis contributes to alterations in fungal pathogenicity during microevolution remains unclear. In this study, we investigated the role of pyroptosis in the pathogenicity of Trichosporon asahii (T. asahii) intraspecies variation, as well as the underlying mechanisms. An in vitro model was established by co-culturing a strain (Ori 2.2174) and a intraspecies variation (Evo 1403.3) of T. asahii with mouse macrophages, while an in vivo model was developed by inoculating immunosuppressed ICR mice with these strains. Survival analysis was performed to assess mortality differences between groups. In vitro experiments revealed that the macrophages infected with Evo 1403.3 exhibited significantly lower lysis rates, pyroptosis levels, and inflammatory cytokine production compared to those infected with Ori 2.2174. Similarly, mice inoculated with Evo 1403.3 showed significantly higher survival rates and reduced fungal burden and lesion areas in organ tissues compared to those infected with Ori 2.2174. Furthermore, pyroptosis mediated by the NLRP3/Caspase-1/GSDMD signaling axis was observed in macrophages infected with both strains, with the extent of pyroptosis positively correlating with strain pathogenicity. Collectively, these findings indicate that cell pyroptosis mediated through the NLRP3/Caspase-1/GSDMD pathway plays a pivotal role in regulating the pathogenicity of T. asahii intraspecies variation.