Shared TIR enzymatic functions regulate cell death and immunity across the tree of life

• Published in: Science (American Association for the Advancement of Science) Vol. 377; no. 6605; p. eabo0001
• Main Authors: Essuman, Kow, Milbrandt, Jeffrey, Dangl, Jeffery L., Nishimura, Marc T.
• Format: Journal Article
• Language: English
• Published: Washington The American Association for the Advancement of Science 29-07-2022
• Subjects: Adaptive systems; Adaptor proteins; Adenine; Adenosine monophosphate; Aging; Amyotrophic lateral sclerosis; Animals; Apoptosis; Archaea; Axons; Bacteria; Bacterial diseases; Bacterial infections; Cell death; Cyclic AMP; Cyclic GMP; Cytokines; Degeneration; Deoxyribonucleic acid; DNA; DNA repair; Environmental effects; Enzymatic activity; Enzymes; Evolutionary conservation; Feedback (Response); Hydrolase; Immune response; Immune system; Immunity; Interleukin 1; Leucine; Macromolecules; Mammals; Metabolism; Mortality; NAD; Neurodegeneration; Neurodegenerative diseases; Nicotinamide adenine dinucleotide; Nucleic acids; Nucleotides; Pathogenesis; Pathogens; Phages; Plant diseases; Prokaryotes; Proteins; Receptor mechanisms; Second messengers; Signal transduction; Survival
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.abo0001

In the 20th century, researchers studying animal and plant signaling pathways discovered a protein domain that is shared across diverse innate immune systems: the Toll/interleukin-1/resistance gene (TIR) domain. The TIR domain is found in several protein architectures and was defined as an adaptor that mediates protein-protein interactions in animal innate immunity and developmental signaling pathways. However, studies of nerve degeneration in animals—and subsequent breakthroughs in plant, bacterial, and archaeal systems—revealed that TIR domains possess enzymatic activities. We provide a synthesis of TIR functions and the role of various related TIR enzymatic products in evolutionarily diverse immune systems. These studies may ultimately guide interventions that would span the tree of life, from treating human neurodegenerative disorders and bacterial infections to preventing plant diseases.
Dealing with pathogens is a constant struggle for many life-forms, and innate and adaptive immune systems are needed to support survival. Essuman
et al
. reviewed the latest insights into the Toll/interleukin-1 resistance/receptor (TIR) domain proteins, which support immune responses across the tree of life, from archaea to bacteria to plants to humans. TIR domains function in innate immune signaling pathways, as well as in axon degeneration in animals. Some, but not all, TIR domains have enzymatic activity. TIR nicotinamide adenine dinucleotide hydrolase activity starves phages as they infect prokaryotes and promotes hypersensitive cell death in a plant’s response to pathogens. Plant TIR domains can also synthesize small, nucleotide-based second messengers that initiate an immune response. —PJH
A review explains that shared enzymatic functions in innate immunity build diverse immune systems from archaea to bacteria to plants to humans.