Abstract
Microbial pathogens possess an arsenal of strategies to invade their hosts, evade immune defences and promote infection. In particular, bacteria use virulence factors, such as secreted toxins and effector proteins, to manipulate host cellular processes and establish a replicative niche. Survival of eukaryotic organisms in the face of such challenge requires host mechanisms to detect and counteract these pathogen-specific virulence strategies. In this Review, we focus on effector-triggered immunity (ETI) in metazoan organisms as a mechanism for pathogen sensing and distinguishing pathogenic from non-pathogenic microorganisms. For the purposes of this Review, we adopt the concept of ETI formulated originally in the context of plant pathogens and their hosts, wherein specific host proteins ‘guard’ central cellular processes and trigger inflammatory responses following pathogen-driven disruption of these processes. While molecular mechanisms of ETI are well-described in plants, our understanding of functionally analogous mechanisms in metazoans is still emerging. In this Review, we present an overview of ETI in metazoans and discuss recently described cellular processes that are guarded by the host. Although all pathogens manipulate host pathways, we focus primarily on bacterial pathogens and highlight pathways of effector-triggered immune defence that sense disruption of core cellular processes by pathogens. Finally, we discuss recent developments in our understanding of how pathogens can evade ETI to overcome these host adaptations.
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Change history
10 February 2020
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Acknowledgements
We thank members of the Brodsky and Shin laboratories for scientific discussion. We thank J. Kagan for scientific discussion and critical reading. Work in the Brodsky laboratory is supported by NIH/NIAID grants AI128530, AI139102 and AI135421. Work in the Shin laboratory is supported by NIH/NIAID grants AI118861 and AI123243, and the Linda Pechenik Montague Investigator Award from the University of Pennsylvania Perelman School of Medicine. Both I.E.B. and S.S. are recipients of the Burroughs-Wellcome Fund Investigators in the Pathogenesis of Infectious Disease Award. N.N. is a recipient of the American Heart Association Predoctoral Fellowship. N.L.F. is a recipient of the Institutional Ruth L. Kirschstein National Research Service Award T32GM07229 and the HHMI James H. Gilliam, Jr. Fellowship for Advanced Study.
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I.E.B. and S.S. developed the initial concept for the Review and conducted the literature search with N.L.F. and N.N.; N.L.F. and N.N. contributed equally to the writing of the manuscript. All authors contributed to revision and editing of the manuscript.
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Lopes Fischer, N., Naseer, N., Shin, S. et al. Effector-triggered immunity and pathogen sensing in metazoans. Nat Microbiol 5, 14–26 (2020). https://doi.org/10.1038/s41564-019-0623-2
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DOI: https://doi.org/10.1038/s41564-019-0623-2
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