Summary Arabidopsis basal immunity depends on cooperation between EDS1-PAD4 dimers and ADR1-family helper NLRs to limit pathogen infection. We investigated the genetic and functional relationships of rice ( Oryza sativa ) EDS1, PAD4 and ADR1 orthologs in disease resistance. Single and combinatorial eds1 , pad4 and adr1 CRISPR/Cas9 mutants were generated in O. sativa ssp . japonica varieties Kitaake and Zhonghua 11. Growth, physiological fitness and disease resistance phenotypes were assessed together with RNA expression and phytohormone profiles. Contributions of EDS1 , PAD4 and ADR1 to resistance against fungal and bacterial pathogens suggest these components also cooperate in promoting rice basal immunity. However, combined loss of EDS1 with PAD4 leads to ADR1 -dependent reduced growth and fitness of rice plants accompanied by constitutively high salicylic acid accumulation and enhanced resistance. The eds1 pad4 double mutant displays features of imbalanced defense - nutrient homeostasis. Data reveal both cooperative and antagonistic EDS1 , PAD4 and ADR1 activities in rice. In pathogen-challenged rice plants, EDS1-PAD4-ADR1 likely function together as a module conferring basal immunity. In pathogen-unchallenged plants, EDS1 and PAD4 individually constrain ADR1 activity, thereby suppressing immune responses and maintaining fitness. ADR1 -dependent autoimmunity in rice eds1 pad4 plants indicates a different mode of ADR1 recruitment and action than via EDS1-PAD4.

Immune regulators EDS1 and PAD4 constrain ADR1-dependent disease resistance in rice