Intracellular innate immune
surveillance devices in plants
Jonathan D. G. Jones,*† Russell E. Vance,*† Jeffery L. Dangl*†
BACKGROUND: Pathogens cause agricultural
devastation and huge economic losses. Up to 30%
of our crops are lost before or after harvest to pathogens and pests, wasting water and human effort.
Diseases and pests are major problems for sustainable agriculture in the face of population growth.
Similarly, microbial infection remains a major
cause of human mortality and morbidity, responsible for ~25% of deaths worldwide in 2012. We
lack vaccines for several major infectious diseases,
and antibiotic resistance is an ever-growing concern.
Plant and animal innate immune systems
(NACHT) domain class, respectively. Animals
respond to pathogen infection and regulate
beneficial interactions with commensal and
symbiotic microbes. Plants and animals use
intracellular proteins of the nucleotide binding
domain (NBD), leucine-rich repeat (NLR) super-
family to detect many kinds of pathogens. Plant
and animal NLRs evolved from distinct deriv-
atives of a common ancestral prokaryotic adeno-
sine triphosphatase (ATPase): the NBD shared
by APAF-1, plant NLR proteins, and CED-4 (NB-
ARC) domain class and that shared by apoptosis
inhibitory protein (NAIP), CIITA, HET-E, TP1
and fungi can carry both NB-ARC and NACHT
domain proteins, but NACHT domain proteins
are absent from plants and several animal taxa,
such as Drosophila and nematodes. Despite the
vast evolutionary distance between plants and
animals, we describe trans-kingdom principles of
NLR activation. We propose that NLRs evolved
for pathogen-sensing in diverse organisms because the flexible protein domain architecture
surrounding the NB-ARC and NACHT domains
facilitates evolution of “hair trigger” switches,
into which a virtually limitless number of microbial detection platforms can be integrated.
ADVANCES: Structural biology is beginning to
shed light on pre- and postactivation NLR architectures. Various detection and activation platforms have evolved in both plant and animal
NLR surveillance systems. This spectrum ranges
from direct NLR activation, through binding of
microbial ligands, to indirect NLR activation after
the modification of host
cellular targets, or decoys
of those targets, by microbial virulence factors. Homo- and heterotypic
dimerization and oligomerization of NLRs add
complexity to signaling responses and can enable
signal amplification. NLR population genomics
across the plant and animal kingdoms is increasing owing to application of new capture-based sequencing methods. A more complete
catalog of NLR repertoires within and across
species will provide an enhanced toolbox for exploiting NLRs to develop therapeutic interventions.
OUTLOOK: Despite breakthroughs in our molecular understanding of NLR activation, many
important questions remain. Biochemical mechanisms of NLR activation remain obscure. Events
downstream of plant NLR activation and outputs such as transcription of defense genes,
changes in cell permeability, localized cell death,
and systemic signaling remain opaque. We do
not know whether activated plant NLRs oligomerize or, if they do, how this is achieved, given
the diversity of subcellular sites of activation observed for various NLRs. It is not clear whether
and how the different N-terminal domains of plant
NLRs signal. We have increasing knowledge regarding how animal NLRs assemble and signal,
although knowledge gaps remain. Therapeutic interventions in humans targeting NLRs remain on
the horizon. Design of novel recognition capabilities and engineering of new or extended NLR
functions to counter disease in animals and plants
provides tantalizing future goals to address plant
and animal health problems worldwide.▪
NLR tree. Evolution of NLR genes followed diverging pathways for plant and animal species.
Numbers of NLR genes per genome identified computationally range widely, as shown on this
stylized evolutionary tree (branches not to scale). The numbers of NLRs can vary markedly even
across genomes from closely related taxa. NLRs likely derived from a common ancestor that
expressed both NACHT and NB-ARC type NBDs. NACHT is found in animal NLRs, and NB-ARC in
plant NLRs. Both occur in fungi. A variety of N- and C-terminal domains have been evolutionarily
recruited onto NBDs, including those characteristic of NLRs. The asterisk for tomato indicates that
experimental evidence exists to give this precision, as discussed in the main text. The double
asterisk for wheat indicates the number of NLRs per diploid genome (wheat is hexaploid). NLR-like fungal proteins lack the LRR domain characteristic of NLRs and are thus not included here.
The list of author affiliations is available in the full article online.
*These authors contributed equally to this work.
†Corresponding author. Email: jonathan.jones@sainsbury-laboratory.
ac.uk (J.D.G.J.); firstname.lastname@example.org (R.E.V.); dangl@email.
Cite this article as J. D. G. Jones et al., Science 354,
aaf6395 (2016). DOI: 10.1126/science.aaf6395
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