International Journal of Molecular Sciences Review Recent Advances in Effector-Triggered Immunity in Plants: New Pieces in the Puzzle Create a Different Paradigm Quang-Minh Nguyen 1,† , Arya Bagus Boedi Iswanto 1,† , Geon Hui Son 1 and Sang Hee Kim 1,2,* 1 Division of Applied Life Science (BK21 Four Program), Plant Molecular Biology and Biotechnology Research Center, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Korea; [email protected] (Q.-M.N.); [email protected] (A.B.B.I.); [email protected] (G.H.S.) 2 Division of Life Science, Gyeongsang National University, 501 Jinju-daero, Jinju 52828, Korea * Correspondence: [email protected] † These authors contributed equally to this work. Abstract: Plants rely on multiple immune systems to protect themselves from pathogens. When pattern-triggered immunity (PTI)—the first layer of the immune response—is no longer effective as a result of pathogenic effectors, effector-triggered immunity (ETI) often provides resistance. In ETI, host plants directly or indirectly perceive pathogen effectors via resistance proteins and launch a more robust and rapid defense response. Resistance proteins are typically found in the form of nucleotide- binding and leucine-rich-repeat-containing receptors (NLRs). Upon effector recognition, an NLR undergoes structural change and associates with other NLRs. The dimerization or oligomerization of NLRs signals to downstream components, activates “helper” NLRs, and culminates in the ETI response. Originally, PTI was thought to contribute little to ETI. However, most recent studies revealed crosstalk and cooperation between ETI and PTI. Here, we summarize recent advancements Citation: Nguyen, Q.-M.; Iswanto, in our understanding of the ETI response and its components, as well as how these components A.B.B.; Son, G.H.; Kim, S.H. Recent Advances in Effector-Triggered cooperate in the innate immune signaling pathways. Based on up-to-date accumulated knowledge, Immunity in Plants: New Pieces in this review provides our current perspective of potential engineering strategies for crop protection. the Puzzle Create a Different Paradigm. Int. J. Mol. Sci. 2021, 22, Keywords: pathogen; effector; PTI; ETI; NLR; plant immunity 4709. https://doi.org/10.3390/ ijms22094709 Academic Editor: Lars Matthias Voll 1. Introduction Plants and pathogens continually compete for supremacy as they coevolve. In nature, Received: 25 March 2021 many plants are resistant to most pathogens, but some pathogenic microbes are capable of Accepted: 27 April 2021 causing severe diseases. The primary barrier of plants against pathogenic invasion is the Published: 29 April 2021 preformed defense layer, including the plant cell wall and pre-produced metabolites [1–4]. To successfully respond to and defend against pathogenic microbes, plants developed Publisher’s Note: MDPI stays neutral multilayered protective and surveillance networks [5]. The first layer of the plant immune with regard to jurisdictional claims in system is pattern-triggered immunity (PTI), which is activated by pathogen-associated published maps and institutional affil- molecular patterns (PAMPs), the conserved molecular structures of pathogens such as iations. fungal chitin or bacterial flagellin, or damage-associated molecular patterns, which are molecules resulting from plant–pathogen interactions such as peptides and oligosaccha- rides (Figure1). These inducers can be recognized by pattern recognition receptors (PRRs), plasma membrane-localized plant immune receptors, which are mainly found in the forms Copyright: © 2021 by the authors. of receptor-like protein kinases and receptor-like proteins [6–8]. Activation of these receptors Licensee MDPI, Basel, Switzerland. provokes an array of plant defense responses to halt pathogen spread and colonization [9,10]. This article is an open access article PTI activates multiple signaling pathways in the host cells (Figure1). One of the rapid re- distributed under the terms and sponses is an influx of extracellular Ca2+ into the cytosol [11–13], followed by the activation conditions of the Creative Commons Attribution (CC BY) license (https:// of mitogen-activated protein kinases [14,15], reactive oxygen species (ROS) signaling [12,16], creativecommons.org/licenses/by/ and other signaling molecules, such as reactive nitrogen species, lipids, callose, salicylic 4.0/). acid, n-hydroxypipecolic acid, jasmonic acid, ethylene, and cytokinin [17–29]. However, Int. J. Mol. Sci. 2021, 22, 4709. https://doi.org/10.3390/ijms22094709 https://www.mdpi.com/journal/ijms Int. J. Mol. Sci. 2021, 22, x FOR PEER REVIEW 2 of 17 Int. J. Mol. Sci. 2021, 22, 4709 2 of 17 gen species (ROS) signaling [12,16], and other signaling molecules, such as reactive nitro- gen species, lipids, callose, salicylic acid, n-hydroxypipecolic acid, jasmonic acid, ethylene, toand defeat cytokinin PTI responses, [17–29]. However, many pathogens to defeat deploy PTI responses, a variety many of effector pathogens proteins deploy (Figure a vari-1). Whenety of they effector are recognizedproteins (Figure by specialized 1). When receptorsthey are recognized in the plant by called specialized resistance receptors (R) pro- in teins,the plant the second called layerresistance of plant (R immune) proteins, responses the second is activated, layer of whichplant immune is effector-triggered responses is immunityactivated, (ETI) which [30 is,31 effector]. -triggered immunity (ETI) [30,31]. FigureFigure 1. 1.Schematic Schematic view view of of pattern-triggered pattern-triggered immunity immunity (PTI) (PTI) and and effector-triggered effector-triggered immunity immunity (ETI) (ETI) in plants. The first layer of induced immunity, called PTI (indicated by black arrows), is activated in plants. The first layer of induced immunity, called PTI (indicated by black arrows), is activated by by the recognition of pathogen-associated molecular patterns (PAMPs) or damage-associated mo- the recognition of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular lecular patterns (DAMPs) through pattern recognition receptors (PRRs). Several PTI signaling patternsevents occur, (DAMPs) such through as activati patternon of recognition the mitogen receptors-activated (PRRs). protein Several kinases PTI (MAPK signaling) kinase events cascades, occur, suchan influx as activation of Ca2+ into of the the mitogen-activated cytosol, and production protein of kinases reactive (MAPK) oxygen kinase species cascades, (ROS). Antimicrobial an influx of Cacompounds2+ into the cytosol,are produced and production and the defense of reactive genes oxygen are activated. species However, (ROS). Antimicrobial to suppress PTI, compounds the path- areogens produced deploy and effectors. the defense When genes they areare activated.recognized However, by nucleotide to suppress-binding PTI, (NB the) and pathogens leucine deploy-rich-re- effectors.peat (LRR When)-containing they are receptors recognized (NLRs by) nucleotide-binding, the second immune (NB) layer, and called leucine-rich-repeat ETI (indicated (LRR)-by blue containingarrows), takes receptors place. (NLRs), NLRs directly the second or indirectly immune layer,perceive called pathogenic ETI (indicated effectors, by blue leading arrows), to a confor- takes place.mational NLRs change directly, which or indirectly together perceive with several pathogenic intracellular effectors, signaling leading events to a conformational, ultimately trigger change, the hypersensitive response (HR) or other defense responses. Surprisingly, the most recent studies re- which together with several intracellular signaling events, ultimately trigger the hypersensitive ported that PTI and ETI are mutually linked and together potentiate the immune response (indi- response (HR) or other defense responses. Surprisingly, the most recent studies reported that PTI cated by red arrows). and ETI are mutually linked and together potentiate the immune response (indicated by red arrows). Structural and functional analysis in current studies of many R proteins reveals that Structural and functional analysis in current studies of many R proteins reveals that there there are two conserved features, nucleotide-binding (NB) and leucine-rich repeat (LRR) are two conserved features, nucleotide-binding (NB) and leucine-rich repeat (LRR) domains, domains, known as NLRs. The structure of other NLR domains depends on whether a known as NLRs. The structure of other NLR domains depends on whether a Toll-interleukin Toll-interleukin 1-like receptor (TIR) or a coiled-coil (CC) is attached at the N terminus 1-like receptor (TIR) or a coiled-coil (CC) is attached at the N terminus (Figure1) [ 32,33]. Host(Figure plants 1) [32,33]. employ Host a diverse plants family employ of a NLRs diverse to detectfamily effectors of NLRs rapidly to detect during effectors pathogen rapidly invasion.during pathogen NLRs selectively invasion. recognize NLRs selectively the effectors, recognize either the directly effectors or, indirectly, either directly and suchor in- recognitiondirectly, and often such leads recognition to a hypersensitive often leads response, to a hypersensitive a form of rapid response, localized a programmedform of rapid celllocalized death (Figureprogrammed1)[ 28 ,cell34,35 death]. The (Figure immune 1) [28,34,35 responses]. The elicited immune by PRRs responses andNLRs elicited are by similar,PRRs and although NLRs the are duration similar, andalthough amplitude the duration of ETI responses and amplitude