Effector‐Triggered Immune Pathologies in Plants

The original Zig‐Zag model applies well to biotrophic plant–pathogen interactions, but is less
applicable to processes involving necrotrophs, i.e. pathogens that feed on dead host tissues. In
contrast with biotrophs, necrotrophic pathogens do not differentiate sophisticated, specialized
infection‐related structures, but instead deploy a multitude of compounds to attack the plant host.
It was assumed that these pathogens operate through ‘brute force attacks’, and that physiological
interactions with the host are limited. However, there is now increasing evidence that
necrotrophs develop stealthy and subtle infection strategies, which, in turn, promote
sophisticated cellular and molecular responses in the plant host.

Necrotrophic fungi from the order Pleosporales (such as Alternaria, Cochliobolus and
Pyrenophora spp.) produce host‐specific toxins (HSTs), which exert their effects on a single
plant species, or a particular cultivar within a given species that expresses a corresponding
‘susceptibility’ gene. HSTs direct host pathways towards PCD, which exclusively benefits the
fungus. PCD signalling pathways are multiple, and well described for mammalian cells. Here,
autophagy and apoptotic processes play key roles during growth and development, and in
response to biotic stimuli. Some individual players in the autophagic and apoptotic signalling
pathways are also involved in plant PCD during both compatible and incompatible host–
pathogen interactions. Others, such as bona fide caspases, are absent from plant cells. However,
the plant Vacuolar Processing Enzyme γ (VPEg) exhibits caspase‐1‐like activities in plant
systems. The proteolytic activity of VPEg is suppressed by caspase‐1‐specific inhibitors, and is
necessary for cell death induction by a wide range of pathogens. The mechanisms involved in
autophagic and apoptotic PCD are thus still subject to heated discussion (for a review, see
Dickman and Fluhr, 2013). However, different cell death pathways can be activated during the
genotype‐dependent interaction of a host plant with a fungal invader. The recognition of fungal
infection by the plant results in host‐controlled PCD with limited cell death and immunity (ETI),
whereas pathogen‐mediated PCD suppresses recognition by the host, thus promoting spreading
cell death, pathogen proliferation and disease.

An interesting example is provided by the HST victorin, which is secreted by the fungus
Cochliobolus victoriae, the causal agent of the Victoria blight of oats. Pathogenesis by C.
victoriae is determined by the production of the cyclic peptide victorin, which activates R
protein‐mediated ETI to cause cell death. Victoria blight exclusively appeared on oat plants
carrying the R gene Pc‐2, which is associated with disease resistance to the biotrophic rust
fungus Puccinia coronata. The sensitivity of oat to victorin is controlled by a single dominant
allele at the Vb locus. Extensive genetic and mutational analyses were not able to separate this
locus from the rust resistance locus Pc‐2, suggesting that Vb and Pc‐2 were the same or closely
linked loci (Mayama et al., 1995). The mechanisms underlying the induction of PCD by victorin
have not yet been elucidated, but our understanding of the interaction was helped by the
identification of a member of the Nod‐like nucleotide‐binding (NB)‐LRR‐type R protein family,
which is encoded by the Locus Orchestrating Victorin effects 1 (LOV1) in Arabidopsis (Lorang
et al., 2007). This R protein must be present for susceptibility to fungal infection. It induces
several (but not all) disease resistance‐associated responses, indicating that victorin targets a
typical resistance protein, which is usually involved in the recognition of a naturally occurring
pathogen of Arabidopsis thaliana. In oat, the natural host for C. victoriae, the resistance gene
located at the Pc‐2 locus may encode a LOV1‐like target. The Pc‐2/Vb locus might thus be the
canonical example of a gene involved in resistance against a biotroph (P. coronata f. sp. avenae)
that has been targeted by a necrotroph (C. victoriae) to induce susceptibility.

Another example supporting this hypothesis is provided by the proteinaceous HST ToxA, which
is produced by the necrotrophic pathogens Pyrenophora tritici‐repentis and Stagonospora
nodorum, and which targets the wheat R gene product Tsn1. The Tsn1 gene encodes an NB‐LRR
receptor protein required for ToxA sensitivity and disease susceptibility (Faris et al., 2010). This
NB‐LRR protein is very similar to the R protein, RPG5, which confers resistance to the
biotrophic stem rust fungus Puccinia graminis (Brueggeman et al., 2008). As shown with
Pc‐2/Vb and Rpg5/Tsn1, identical NB‐LRRs might be involved in PCD, leading either to ETI
against biotrophs or HST‐triggered susceptibility to necrotrophs.

These two examples provide evidence that ETI, which represents a major source of qualitative
resistance to biotrophs, is subverted by necrotrophs to promote host cell death for nutrient
supply. HSTs probably evolved as an adaptive response to selective pressure induced by plant R
gene products, thus rendering necrotrophic pathogens hypervirulent. Hypervirulent susceptibility
might be considered the outcome of host manipulation to promote pro‐inflammatory infectious
processes that aim to actively kill plant cells for feeding purposes. It is an additional adaptive
ramification of ETI in the Zig‐Zag model, and parallels ETIPs that are induced by toxins in
mammalian cells (Fig. (Fig.11).