The apoplastic protein OsCPIP8 confers dual protection by inhibiting pathogenic protease and activating rice immunity.

Cysteine proteases play key roles in plant immunity. In contrast, pathogen-secreted proteases contribute to destroying the immune defenses of plants and animals. However, the pathogenic mechanism remains enigmatic. Here, we find Xanthomonas oryzae pv. oryzicola (Xoc)-secreted cysteine proteinase XoCysP1 interacts with rice-secreted xylanase inhibitory protein OsXIP2, which enhances rice resistance to Xoc, and promotes OsXIP2 degradation in rice apoplast. As a counterattack, the rice-secreted cysteine protease inhibitory protein OsCPIP8 associates with XoCysP1 to block XoCysP1-mediated OsXIP2 degradation and confer rice resistance. Additionally, OsCPIP8 is recognized by the receptor-like kinases OsRLK8 and OsSERK2 to trigger plant immunity. In conclusion, OsCPIP8 not only protects defense protein OsXIP2 from degradation by the pathogen but also activates rice immunity recognized by receptors. This discovery will enhance the understanding of "attack and defense" mechanisms between pathogens and hosts in the apoplast, and provide a roadmap for developing biopesticides and pathogen-informed resistant crops.