A protein domain (Toll and Interleukin-1 receptor [TIR]-like) with homology to animal TIRs mediates immune signaling in prokaryotes and eukaryotes. Here, we present an overview of TIR evolution and the molecular versatility of TIR domains in different protein architectures for host protection against microbial attack. Plant TIR-based signaling emerges as being central to the potentiation and effectiveness of host defenses triggered by intracellular and cell-surface immune receptors. Equally relevant for plant fitness are mechanisms that limit potent TIR signaling in healthy tissues but maintain preparedness for infection. We propose that seed plants evolved a specialized protein module to selectively translate TIR enzymatic activities to defense outputs, overlaying a more general function of TIRs.

TIR signaling promotes the interactions between lipase-like proteins EDS1/PAD4 and ADR1-L1 immune receptor, and oligomerization of ADR1-L1.

Both plants and animals utilize nucleotide-binding leucine-rich repeat immune receptors (NLRs) to perceive the presence of pathogen-derived molecules and induce immune responses. NLR genes are far more abundant and diverse in vascular plants than in animals. Truncated NLRs, which lack one or more of the canonical domains, are also commonly encoded in plant genomes. However, little is known about their functions, especially the N-terminally truncated ones. Here, we show that the Arabidopsis thaliana N-terminally truncated helper NLR (hNLR) gene N REQUIREMENT GENE1 (NRG1C) is highly induced upon pathogen infection and in autoimmune mutants. The immune response and cell death conferred by some Toll/interleukin-1 receptor-type NLRs (TNLs) were compromised in Arabidopsis NRG1C overexpression lines. Detailed genetic analysis revealed that NRG1C antagonizes the immunity mediated by its full-length neighbors NRG1A and NRG1B. Biochemical tests suggested that NRG1C might interfere with the EDS1–SAG101 complex, which functions in immunity signaling together with NRG1A/1B. Interestingly, Brassicaceae NRG1Cs are functionally exchangeable and that the Nicotiana benthamiana N-terminally truncated hNLR NRG2 also antagonizes NRG1 activity. Together, our study uncovers an unexpected negative role of N-terminally truncated hNLRs in immunity in different plant species.