Toxoplasma gondii induces MST2 phosphorylation mediating the activation of hippo signaling pathway to promote apoptosis and lung tissue damage

<i>Toxoplasma gondii</i> (<i>T. gondii</i>) is an intracellular parasite, and its regulation of host cell apoptosis directly affects its parasitism. Studies link <i>T. gondii</i>-induced apoptosis to abnormal expression of mammalian STE20-like protein kinase 2 (MST2), but its precise role remains unclear. In this study, the regulatory roles in apoptosis and pathogenicity of <i>T. gondii</i> infection were identified <i>in vitro</i> and <i>in vivo</i>. Simultaneously, MST2 and Hippo signaling pathway activation induced by <i>T. gondii</i> were evaluated. MST2 overexpression and knockout were used to assess its regulatory role in apoptosis and Hippo signaling pathway. Results showed that <i>T. gondii</i> induced apoptosis and lung damage, with Hippo signaling pathway activation via MST2 phosphorylation. MST2 was demonstrated to regulate apoptosis and Hippo signaling pathway. Notably, MST2 knockout hindered the <i>T. gondii</i>-induced apoptosis and weakened Hippo signaling pathway activation. MST2 is an important target for <i>T. gondii</i> to control host cell fate and modulate immune responses.