The article by Daniel Couto and Cyril Zipfel provides an in-depth review of the regulation of pattern recognition receptor (PRR) signaling in plants. PRRs are crucial for plant innate immunity, recognizing pathogen-derived molecules such as pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The activation of PRRs initiates immune responses at the cell surface through kinase complexes, leading to the activation of downstream signaling pathways. However, the amplitude and duration of these responses must be tightly controlled to prevent excessive or untimely activation, which can lead to autoimmune diseases in both plants and animals. The review covers several key aspects of PRR signaling regulation: 1. **Formation and Activation of PRR Complexes**: PRRs form dynamic complexes with regulatory receptor kinases (RRKs) and receptor-like cytoplasmic kinases (RLCKs) to initiate signaling. These complexes are recruited by ligands and can be regulated by pseudokinases and protein phosphatases. 2. **Activation of Cellular Immune Signaling**: Upon PRR activation, a branched signaling cascade is initiated, leading to rapid ion flux changes, cytosolic Ca²⁺ increases, and production of reactive oxygen species (ROS). These events trigger transcriptional reprogramming and the production of antimicrobial compounds. 3. **Negative Regulation of PRR-Mediated Immunity**: To maintain immune homeostasis, plants employ various strategies to adjust the amplitude and duration of PRR-mediated responses. These include limiting PRR complex recruitment, regulating signaling initiation and amplitude, monitoring cytoplasmic signal transducing pathways, and controlling transcriptional reprogramming. 4. **Regulation by Hormones and Endogenous Peptides**: Plant hormones, such as salicylic acid, jasmonic acid, and ethylene, play crucial roles in integrating external and internal cues to maintain homeostasis and coordinate immune responses. Endogenous peptides like PSKα and PSY1 also negatively regulate several PRR-mediated responses. The authors highlight the complexity and tight regulation of PRR-triggered immunity, emphasizing the importance of understanding the molecular mechanisms underlying immune signaling at the cell surface. They also discuss how pathogens manipulate these systems to suppress plant immunity, providing insights into potential strategies for engineering disease resistance in crops.The article by Daniel Couto and Cyril Zipfel provides an in-depth review of the regulation of pattern recognition receptor (PRR) signaling in plants. PRRs are crucial for plant innate immunity, recognizing pathogen-derived molecules such as pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The activation of PRRs initiates immune responses at the cell surface through kinase complexes, leading to the activation of downstream signaling pathways. However, the amplitude and duration of these responses must be tightly controlled to prevent excessive or untimely activation, which can lead to autoimmune diseases in both plants and animals. The review covers several key aspects of PRR signaling regulation: 1. **Formation and Activation of PRR Complexes**: PRRs form dynamic complexes with regulatory receptor kinases (RRKs) and receptor-like cytoplasmic kinases (RLCKs) to initiate signaling. These complexes are recruited by ligands and can be regulated by pseudokinases and protein phosphatases. 2. **Activation of Cellular Immune Signaling**: Upon PRR activation, a branched signaling cascade is initiated, leading to rapid ion flux changes, cytosolic Ca²⁺ increases, and production of reactive oxygen species (ROS). These events trigger transcriptional reprogramming and the production of antimicrobial compounds. 3. **Negative Regulation of PRR-Mediated Immunity**: To maintain immune homeostasis, plants employ various strategies to adjust the amplitude and duration of PRR-mediated responses. These include limiting PRR complex recruitment, regulating signaling initiation and amplitude, monitoring cytoplasmic signal transducing pathways, and controlling transcriptional reprogramming. 4. **Regulation by Hormones and Endogenous Peptides**: Plant hormones, such as salicylic acid, jasmonic acid, and ethylene, play crucial roles in integrating external and internal cues to maintain homeostasis and coordinate immune responses. Endogenous peptides like PSKα and PSY1 also negatively regulate several PRR-mediated responses. The authors highlight the complexity and tight regulation of PRR-triggered immunity, emphasizing the importance of understanding the molecular mechanisms underlying immune signaling at the cell surface. They also discuss how pathogens manipulate these systems to suppress plant immunity, providing insights into potential strategies for engineering disease resistance in crops.