An effector from the potato late blight pathogen hijacks the host ESCRT pathway to suppress an NLR/PRR immune receptor network

Plant nucleotide-binding leucine-rich repeat (NLR) proteins are critical components of the plant immune system that recognize and respond to pathogen attacks. Upon immune activation, NLRs form higher order complexes termed resistosomes. Parasites can counteract host immunity by suppressing helper NLR proteins that function as central nodes in immune receptor networks. We previously reported that the Phytophthora infestans effector AVRcap1b can suppress cell death mediated cell surface and intracellular immune receptors by targeting helper NLRs NRC2/3. AVRcap1b associates with host NbTOL9a, a protein involved in ESCRT mediated vesicle trafficking, which acts as a negative regulator of NRC signaling. NbTOL9a is genetically required for full AVRcap1b immune suppression. The precise mechanism by which AVRcap1b suppresses NRCs is not fully understood. Here we obtained the crystal structure of AVRcap1b bound to the N-terminal ENTH domain of NbTOL9a. Mutating the AVRcap1b-NbTOL9a binding interface abolishes AVRcap1b immune suppression. We show that while AVRcap1b does not suppress NRC oligomerization, it specifically associates with activated, but not inactive, NRC2. We propose that AVRcap1b bridges the host ESCRT trafficking machinery and activated NRC2 complexes to suppress NRC-mediated cell death. Our results provide insights into how plant parasites can inhibit NLR-mediated signaling resulting in a broad suppression of both cell surface and intracellular immunity.