Plants deploy intracellular receptors to counteract pathogen effectors that suppress cell-surface-receptor-mediated immunity. To what extent pathogens manipulate intracellular receptor-mediated immunity, and how plants tackle such manipulation, remains unknown. Arabidopsis thaliana encodes three similar ADR1 class helper nucleotide-binding domain leucine-rich repeat receptors (ADR1, ADR1-L1, and ADR1-L2), which are crucial in plant immunity initiated by intracellular receptors. Here, we report that Pseudomonas syringae effector AvrPtoB suppresses ADR1-L1- and ADR1-L2-mediated cell death. ADR1, however, evades such suppression by diversifying into two ubiquitination sites targeted by AvrPtoB. The intracellular sensor SNC1 interacts with and guards the CCR domains of ADR1-L1/L2. Removal of ADR1-L1/L2 or delivery of AvrPtoB activates SNC1, which then signals through ADR1 to trigger immunity. Our work elucidates the long-sought-after function of SNC1 in defense, and also how plants can use dual strategies, sequence diversification, and a multi-layered guard-guardee system, to counteract pathogen\'s attack on core immunity functions.

Nucleotide-binding leucine-rich repeat (NLR) proteins are intracellular immune receptors that restrict plant invasion by pathogens. Most NLRs operate in intricate networks to detect pathogen effectors in a robust and efficient manner. NLRs are not static sensors; rather, they exhibit remarkable mobility and structural plasticity during the innate immune response. Inactive NLRs localize to diverse subcellular compartments where they are poised to sense pathogen effectors. During pathogen attack, some NLRs relocate toward the plant-pathogen interface, possibly to ensure their timely activation. Activated NLRs reorganize into wheel-shaped oligomers, some of which then form plasma membrane pores that promote calcium influx and programmed cell death. The emerging paradigm is that this variable and dynamic nature underpins effective NLR-mediated immunity.