The first line of defence is mounted by pattern recognition receptors, or PRRs, which sit at the cell surface and detect conserved microbial molecules known as microbe-associated molecular patterns. These include bacterial flagellin, the translation factor EF-Tu, fungal chitin and bacterial peptidoglycan. When a PRR such as the flagellin receptor FLS2 binds its ligand, it recruits a co-receptor kinase called BAK1, forming an active receptor complex that triggers a cascade of phosphorylation events. Structural studies over the past decade have revealed the atomic details of these interactions, showing how ligand binding induces dimerization and allosteric activation of the kinase domains. The review emphasizes that receptor-like proteins, which lack an intracellular kinase domain, rely on partner kinases such as SOBIR1 and BAK1 to transduce signals, and that recent work has clarified how these complexes assemble and activate downstream pathways.

Once a PRR is activated, a receptor-like cytoplasmic kinase called BIK1 is released from the receptor complex and phosphorylates a remarkable range of targets. BIK1 directly activates the NADPH oxidase RbohD, driving a burst of reactive oxygen species that reinforces cell walls and signals to neighbouring cells. It also regulates calcium channels, including CNGCs and OSCA1.3, allowing cytosolic calcium concentrations to rise rapidly. This calcium influx is not merely a byproduct; it is a central hub of immune signalling. Calcium-dependent protein kinases decode the calcium signature and phosphorylate transcription factors and metabolic enzymes, while calcium-activated metacaspases release immunomodulatory peptides from damaged cells. The review highlights how this spatiotemporally controlled calcium symphony, as one group of researchers has described it, links pattern recognition to gene expression, stomatal closure and the production of antimicrobial compounds.

The second branch of plant immunity operates inside the cell. Intracellular nucleotide-binding leucine-rich repeat receptors, or NLRs, detect pathogen effectors, the virulence proteins that pathogens inject into host cells to suppress pattern-triggered immunity. The gene-for-gene concept, articulated by Harold Flor in the 1970s, predicted that for every resistance gene in the plant there is a corresponding avirulence gene in the pathogen. Decades of work have vindicated this idea at the molecular level. Some NLRs directly bind effectors, while others act as guards or decoys, monitoring host proteins that effectors modify. Integrated domains, which are fusions of host target mimics into the NLR architecture, allow single receptors to sense effectors that manipulate specific host processes. The review traces this conceptual evolution from the cloning of the first NLR genes in the 1990s to the recent explosion of structural biology that has revealed how these receptors work.

The most striking recent discovery in this field concerns resistosomes. When certain NLRs recognize their cognate effectors, they do not simply change shape; they oligomerize into large, ordered complexes that function as channels or enzymes. The ZAR1 resistosome, for example, forms a pentameric calcium-permeable channel in the plasma membrane, flooding the cytosol with calcium and triggering cell death at the infection site. Helper NLRs of the NRC and ADR1 families form hexameric resistosomes with similar channel activity, while TIR-domain-containing NLRs act as NAD-cleaving enzymes that produce small signalling molecules. Recent work has shown that helper NLR resistosome clusters assemble upon activation of sensor NLRs, and that a wheat CCG10-NLR receptor forms an octameric resistosome. These structures represent a remarkable convergence with animal immunity, where inflammasomes perform analogous functions, and they explain how a single molecular recognition event can be amplified into a full-scale defensive response.

Perhaps the most important conceptual shift in recent years is the recognition that pattern-triggered immunity and effector-triggered immunity are not separate pathways but mutually reinforcing branches of a single system. Studies published in 2021 demonstrated that PRR signalling is required for full NLR-mediated resistance, and that activation of TIR signalling boosts pattern-triggered responses. The EDS1-PAD4-ADR1 node, a complex of lipase-like proteins and helper NLRs, mediates both branches, providing a molecular bridge between cell surface and intracellular perception. This mutual potentiation means that a plant that has already mounted a pattern-triggered response is primed to respond more vigorously to effector recognition, and vice versa. The review argues that this integration explains why plants with compromised PRR function are often more susceptible to disease even when they possess functional NLR genes.

But immunity is expensive. Uncontrolled activation of PRRs or NLRs causes stunted growth, autoimmunity and reduced seed yield, a phenomenon known as the growth-defence trade-off. Plants have evolved multiple mechanisms to keep immune signalling in check. Negative regulators such as the protein phosphatase PP2C38 dephosphorylate BIK1, while ubiquitin ligases control BIK1 protein homeostasis. The BAK1 co-receptor is shared between immune receptors and the brassinosteroid growth receptor BRI1, creating a molecular competition between defence and growth signalling. BIK1 inversely modulates these two pathways, promoting immunity while suppressing brassinosteroid responses. Membrane nanodomains physically separate immune and growth receptor complexes, even when they share signalling components. The review also describes how phytosulfokine signalling, mediated by the receptor PSKR1, balances growth and defence in the rhizosphere, and how transcription factors such as BZR1 mediate trade-offs at the gene expression level.

Environmental conditions add another layer of complexity. Temperature, light and humidity all modulate immune responses. Elevated temperatures can suppress NLR-mediated resistance, but recent work has identified CBP60g family transcription factors as key determinants of temperature sensitivity, offering a route to climate-resilient immunity. Light quality matters too: the blue-light receptor CRY1 acts as a switch that balances photosynthesis and defence, while phytochromes regulate salicylic acid and jasmonic acid pathways in rice. High humidity dampens salicylic acid signalling and NPR1 function, promoting disease, and daily humidity oscillations entrain the circadian clock to influence plant physiology. The microbiome also plays a role, with rhizosphere bacteria suppressing local root immune responses through pH modulation, and leaf microbiota influencing autoimmunity in Arabidopsis. The review presents a schematic model of these interplays, emphasizing that immunity cannot be understood in isolation from the environment.

The practical implications are profound. Understanding the mechanisms of immune receptor activation and regulation opens the door to engineering disease-resistant crops with optimized fitness. Researchers have transferred PRRs between plant families to confer broad-spectrum bacterial resistance, stacked multiple PRRs in potato against Phytophthora infestans, and used reverse engineering of FLS2 to expand recognition of evasive flagellin epitopes. NLR engineering has progressed from single amino acid mutations that expand effector recognition to designer receptors with novel specificities, nanobody fusions that redirect NLRs to new targets, and interfamily co-transfer of sensor and helper NLR pairs. Genome editing of susceptibility genes has produced multipathogen resistance without agronomic penalty, and inducible overexpression of transcription factors such as Ideal Plant Architecture1 improves both yield and disease resistance in rice. Machine learning and AlphaFold-guided design are now being applied to predict effector targets and redesign immune proteins. The review concludes that the next frontier lies in combining these engineering strategies with a deep understanding of growth-defence balance, so that crops can be made both resistant and productive in a changing climate.

Subject of Research: Mechanisms of pathogen perception, immune signalling and growth-defence balance in plant immunity

Article Title: Mechanisms and balanced regulation of plant immunity

Article References: Chai, J., Wang, Y., & Wang, Y. (2026). Mechanisms and balanced regulation of plant immunity. Nature Reviews Molecular Cell Biology. https://doi.org/10.1038/s41580-026-01009-4

Image Credits: AI Generated

DOI: 10.1038/s41580-026-01009-4

Keywords: plant immunity, pattern recognition receptors, NLR receptors, resistosomes, calcium signalling, growth-defence trade-off, effector recognition, immune receptor engineering, BIK1, BAK1, PTI, ETI

Typically, MADA motif-containing CNLs activate immune responses by directly assembling into homomeric resistosomes that penetrate the plant’s inner plasma membrane, functioning as calcium-permeable channels. These resistosomes offer a direct conduit for Ca^2+ influx, which is critical for initiating programmed cell death and defense mechanisms against pathogens. By contrast, non-MADA CNLs such as SUMM2 and RPS5 employ a distinct activation process. SUMM2, for instance, relies on N-myristoylation—a lipid modification essential for tethering these CNLs to the plasma membrane—and instead promotes the assembly of multiprotein resistosome clusters without forming traditional calcium channels.

More intriguingly, SUMM2’s activation doesn’t appear to involve the direct formation of Ca^2+ channels. Instead, SUMM2 facilitates the organization of higher-order clusters composed of the EDS1–PAD4 signaling module in conjunction with helper NLR proteins like ADR1s. This assembly localizes at the plasma membrane and plays a crucial role in triggering cell death, highlighting an alternative immune activation strategy divergent from classical CNL pore formation.

The study further explores the role of EDS1 (Enhanced Disease Susceptibility 1) protein complexes in two distinct immune signaling branches mediated by Toll-interleukin-1 receptor-like NLRs (TNLs). SUMM2-mediated immunity involves the EDS1–PAD4–ADR1s axis specifically, sparing the EDS1–SAG101 complex. This specificity likely arises from structural variations within the EP domain regions of PAD4 and SAG101, underscoring the molecular intricacies dictating immune receptor interactions and signaling specificity.

TIR enzymatic activity, responsible for the production of downstream nucleotide signaling molecules, appears to be a key factor in the SUMM2-driven EDS1–PAD4–ADR1s pathway. Although other TNLs, such as RPS6, have previously been linked to immune responses involving MEKK1-mediated cell death, their role seems limited or negligible in different Arabidopsis accessions, suggesting a complex and accession-specific immune landscape where multiple TNLs may converge on this signaling pathway.

One of the most profound insights from this work is the dynamic nature of protein interactions during immune activation. SUMM2 seems to sequester the EDS1–PAD4 complex under resting conditions, preventing premature signaling. Upon activation, SUMM2 releases this heterodimer, which then engages with ADR1 helper NLRs to propagate immune signals. This release mechanism mirrors the dynamic interplay observed in TNL engagement of EDS1–SAG101 and helper NRG1 proteins, which form oligomeric complexes essential for immune signaling and programmed cell death.

Using total internal reflection fluorescence (TIRF) microscopy, the researchers observed that SUMM2 activation induces ADR1-L1 oligomerization and the formation of distinctive punctate structures at the cell periphery. These structures often cluster into ring-like patterns resembling assemblies of two to six immobile ADR1-L1 resistosomes. The observed assemblies are substantially larger than the nanoscale pentameric or hexameric CNL resistosomes previously resolved by cryo-electron microscopy, likely reflecting in vivo recruitment of additional host components such as membranes and cytoskeletal elements, contributing to their larger, hydrated architecture.

Importantly, the study highlights a potential two-step model for plant immune-induced cell death that parallels mammalian pyroptosis mechanisms. While plant CNL and helper NLR resistosomes form plasma membrane pores to mediate calcium influx, their pore sizes are considerably smaller than those of mammalian gasdermin pores, which undergo a two-phase process involving initial cytokine release followed by membrane rupture mediated by proteins like NINJ1. Drawing an analogy, plant resistosome clusters incorporating EDS1–PAD4–ADR1-L1 form ring-like assemblies that could induce localized membrane disruption, facilitating the release of cellular contents to complete the cell death program.

Despite these advances, the researchers emphasize the need for direct experimental validation of the proposed model in plants, including the characterization of resistosome clusters’ precise molecular composition and their membrane-disruptive activities. Understanding these mechanisms could unlock new strategies for engineering crop immunity, potentially enabling the development of plants with improved resistance against diverse pathogens.

This work also shines a spotlight on the complex orchestration between sensor NLRs, helper NLRs, and lipid-like signaling complexes, pointing to a finely tuned immune network. The intricacies of this network have far-reaching implications for plant biology, especially in the context of transcriptional defense reprogramming, where EDS1–PAD4–ADR1 signaling plays a central role in activating broad-spectrum immune responses.

The discovery of noncanonical pathways employed by non-MADA CNLs challenges the existing paradigm and encourages a reevaluation of how immune receptors orchestrate defense beyond direct pore formation. Such insights open new frontiers for research into the evolution and diversification of plant immune systems and their underlying molecular machinery.

In conclusion, this seminal study elucidates divergent mechanisms by which plant CNLs regulate immune activation. By revealing the assembly of helper NLR resistosome clusters and their participation in signal transduction, it offers a fresh perspective on plant defense strategies. These findings not only deepen our understanding of plant immunity but also lay the groundwork for future innovations in agriculture and plant biotechnology, heralding a new era in the battle against plant pathogens.

Subject of Research: Plant immune receptor activation mechanisms involving coiled-coil NLRs and helper NLR resistosome cluster assembly.

Article Title: Assembly of helper NLR resistosome clusters upon activation of a coiled-coil NLR.

Article References:
Ge, D., Ortiz-Morea, F.A., Xie, Y. et al. Assembly of helper NLR resistosome clusters upon activation of a coiled-coil NLR. Nature (2026). https://doi.org/10.1038/s41586-026-10215-1

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41586-026-10215-1