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Effector-triggered versus pattern-triggered immunity: how animals sense pathogens

Nature Reviews Immunology volume 13, pages 199–206 (2013)Cite this article

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Abstract

A fundamental question regarding any immune system is how it can discriminate between pathogens and non-pathogens. Here, we discuss how this discrimination can be mediated by a surveillance system distinct from pattern-recognition receptors that recognize conserved microbial patterns. It can be based instead on the ability of the host to sense perturbations in host cells induced by bacterial toxins or 'effectors' that are encoded by pathogenic microorganisms. Such 'effector-triggered immunity' was previously demonstrated mainly in plants, but recent data confirm that animals can also use this strategy.

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Figure 1: An integrated model for detection of pathogenic bacteria.
Figure 2: The outputs of effector-triggered immune responses are specific to the type of initiating damage.
Figure 3: The co-evolution of pathogenic bacteria with the host immune response.

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Acknowledgements

The authors would like to thank E. Lemichez, F. Ausubel, A. Lacy-Hulbert and J. Irazoqui for their helpful discussion and critical reading of the manuscript. N.P. was supported by the US National Institutes of Health (NIH)/US National Institute of Allergy and Infectious Diseases (NIAID) through the New England Regional Center of Excellence (NERCE) (U54 AI057159); L.B. was supported by Ligue Nationale Contre le Cancer, by institutional funding from INSERM and by grants from Fondation Infectiopôle Sud and Fondation ARC pour la Recherche sur le Cancer (ARC SFI 20111203659 and ARC SFI 20121205382); and L.M.S. was supported by grants from NIH/NIAID.

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Authors and Affiliations

  1. Lynda M. Stuart and Nicholas Paquette are at Developmental Immunology/CCIB, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02114, USA.,

    Lynda M. Stuart & Nicholas Paquette

  2. Lynda M. Stuart is also at The Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02142, USA.,

    Lynda M. Stuart

  3. Laurent Boyer is at INSERM, U1065, Centre Méditerranéen de Médecine Moléculaire, C3M, Toxines Microbiennes dans la relation hôte pathogènes, Nice, F-06204, France.,

    Laurent Boyer

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Correspondence to Lynda M. Stuart.

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Glossary

Avirulence gene

(Avr gene). The original plant terminology for genes encoding bacterial effectors that induce effector-triggered immunity in the resistant host.

Damage-associated molecular patterns

(DAMPs). Self-derived immune elicitors that indicate damage to the host. As a result of cellular stress, cellular damage or non-physiological cell death, DAMPs are released from various compartments, including the degraded stroma (in the case of hyaluronate, for example), the nucleus (in the case of high-mobility group protein B1) and the cytosol (in the case of ATP, uric acid, S100 calcium-binding proteins and heat-shock proteins). Such DAMPs are thought to elicit local inflammatory reactions.

Effector-triggered immune pathology

(ETIP). An over-exuberant immune response induced by bacterial effectors that benefits the pathogen and is to the detriment of the host.

Effector-triggered immunity

(ETI). The detection of and response to microbial effectors that enter the host cell and trigger a protective immune response by the host.

Effector-triggered susceptibility

(ETS). Immune suppression or evasion caused by bacterial effectors that enter the host cell and disrupt defence pathways.

IMD innate immune signalling pathway

One of two innate immune NF-κB signalling pathways in Drosophila melanogaster. The IMD pathway responds to DAP-type peptidoglycan from Gram-negative, and some Gram-positive, bacteria. This leads to the rapid and robust production of antimicrobial peptides.

Microorganism-associated molecular patterns

(MAMPs). After the realization that PAMPs are found in both pathogens and non-pathogens, the term MAMPs was suggested as a more appropriate description of the microbial ligands that bind to PRRs.

Pathogen-associated molecular patterns

(PAMPs). The term originally used to describe the immune elicitors found in bacteria, but not in mammalian cells, that bind to PRRs and drive immune responses. Examples include terminally mannosylated and polymannosylated compounds, which bind to the mannose receptor, and various microbial products, such as bacterial lipopolysaccharides, hypomethylated DNA, flagellin and double-stranded RNA, which bind to Toll-like receptors. This term has now been superseded by MAMPs.

Pattern-recognition receptors

(PRRs). Proteins expressed by innate immune cells that detect molecules associated with microbial pathogens or cellular stress.

Pattern-triggered immunity

(PTI). The immune response elicited after the ligation of a PRR by its microbial ligand. A more appropriate term would in fact be MAMP-triggered immunity, for the reasons described above.

Resistance gene

(R gene). The original plant terminology for a host gene encoding a protein that is required for the direct or indirect sensing of a pathogen effector and that elicits a protective immune response.

Sterile inflammation

Inflammation triggered by the danger signals that are induced by chemical or physical stress, in the absence of infection.

Type III secretion system

A specialized molecular machine present in some bacteria that allows the injection of bacterial proteins into host cells.

'Zig-zag' model

A model that was proposed to illustrate the quantitative output of the plant immune system and to explain the co-evolution of plant resistance genes and pathogen effectors.

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Stuart, L., Paquette, N. & Boyer, L. Effector-triggered versus pattern-triggered immunity: how animals sense pathogens. Nat Rev Immunol 13, 199–206 (2013). https://doi.org/10.1038/nri3398

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