Immune responses induced by oligogalacturonides are differentially affected by AvrPto and loss of BAK1/BKK1 and PEPR1/PEPR2

Plants possess an innate immune system capable of restricting invasion by most potential pathogens. At the cell surface, the recognition of microbe‐associated molecular patterns (MAMPs) and/or damage‐associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs) represents the first event for the prompt mounting of an effective immune response. Pathogens have evolved effectors that block MAMP‐triggered immunity. The Pseudomonas syringae effector AvrPto abolishes immunity triggered by the peptide MAMPs flg22 and elf18, derived from the bacterial flagellin and elongation factor Tu, respectively, by inhibiting the kinase function of the corresponding receptors FLS2 and EFR, as well as their co‐receptors BAK1 and BKK1. Oligogalacturonides (OGs), a well‐known class of DAMPs, are oligomers of α‐1,4‐linked galacturonosyl residues, released on partial degradation of the plant cell wall homogalacturonan. We show here that AvrPto affects only a subset of the OG‐triggered immune responses and that, among these responses, only a subset is affected by the concomitant loss of BAK1 and BKK1. However, the antagonistic effect on auxin‐related responses is not affected by either AvrPto or the loss of BAK1/BKK1. These observations reveal an unprecedented complexity among the MAMP/DAMP response cascades. We also show that the signalling system mediated by Peps, another class of DAMPs, and their receptors PEPRs, contributes to OG‐activated immunity. We hypothesize that OGs are sensed through multiple and partially redundant perception/transduction complexes, some targeted by AvrPto, but not necessarily comprising BAK1 and BKK1.     

PEPRs spice up plant immunity

Some pattern recognition receptors (PRRs) in plants, such as PEPRs, sense endogenous, damage‐associated molecular patterns (DAMPs) that are released during pathogen infection. In this issue of The EMBO Journal, Yamada and colleagues show that genetic or pathogen‐induced depletion of Arabidopsis BAK1, a co‐receptor for multiple PRRs, primes immune activation through PEPRs. The work illustrates a link between pathogen‐induced perturbation of BAK1 and DAMP signaling.     

Innate immunity and cardiomyocytes in ischemic heart disease

Myocardial ischemia/reperfusion (I/R) is the most common cause of myocardial inflammation, which is primarily a manifestation of the innate immune responses. Innate immunity is activated when pattern recognition receptors (PRRs) respond to molecular patterns common to microbes and to danger signals expressed by injured or infected cells, so called pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The expression of various PRRs in cardiomyocytes and the release of DAMPs from cardiomyocytes subjected to I/R injury, through active mechanisms as well as passive processes, enable cardiomyocytes to generate innate immune responses. Studies in isolated heart and cardiomyocytes have confirmed the inflammatory and functional effects of cardiac PRRs especially Toll-like receptors in response to I/R-derived DAMPs, such as heat shock proteins. This review addresses the active role of cardiomyocytes in mediating innate inflammatory responses to myocardial I/R. We propose that cardiomyocytes act as innate immune cells in myocardial I/R injury.     

Pattern recognition receptors—Molecular orchestrators of inflammation in inflammatory bowel disease

Pattern recognition receptors (PRRs) are a family of germline encoded receptors responsible for the detection of “pathogen associated molecular patterns” (PAMPs) or host derived “damage associated molecular patterns” (DAMPs) which induce innate immune signalling to generate a pro-inflammatory profile within the host. Four main classes of PRRs are recognised, Toll-like receptors (TLRs), NOD-like receptors (NLRs), RIG-like receptors (RLRs) and C-type lectin receptors (CLRs). Abnormal activation of PRRs has been implicated in various autoimmune and inflammatory conditions including rheumatoid arthritis and asthma. Recent growing evidence has implicated these PRRs as contributory elements to the pathogenesis of inflammatory bowel disease (IBD) and colitis-associated cancer (CAC). Here, the current literature which implicates PRRs in IBD and CAC is comprehensively reviewed.     

Plant Surface Receptors Recognizing Microbe-Associated Molecular Patterns

As sessile, plants are inevitably exposed to environmental threats including pathogens. Due to the lack of mobile immune cells, plants solely depend on the innate immune system to defend against pathogens. The first layer of pathogen detection in plant immunity is to recognize microbe-associated molecular patterns (MAMPs) that compose structural or functional units in microbial pathogens. For this, plants utilize pattern-recognition receptors (PRRs). Continuous attack by pathogens resulting from immotility likely contributes to the extension of PRR numbers in plants, although genomeencoded. Recent findings revealed that plant PRRs as a complex dynamically switch between inactive and active forms at the plasma membrane depending on a cognate MAMP. In addition, by regulating the activity and stability of a downstream signal-relaying receptor-like cytoplasmic kinase (RLCK), plants can control the immune homeostasis. Therefore, we in this review discuss on how plants detect a pathogen and how they control immune responses at the level of PRRs in a correct and delicate way. We additionally provide a possible balancing mechanism between growth and responses to biotic and abiotic stresses in plants, which is required for survival in nature.     

Four Arabidopsis berberine bridge enzyme‐like proteins are specific oxidases that inactivate the elicitor‐active oligogalacturonides

Recognition of endogenous molecules acting as ‘damage‐associated molecular patterns’ (DAMPs) is a key feature of immunity in both animals and plants. Oligogalacturonides (OGs), i.e. fragments derived from the hydrolysis of homogalacturonan, a major component of pectin are a well known class of DAMPs that activate immunity and protect plants against several microbes. However, hyper‐accumulation of OGs severely affects growth, eventually leading to cell death and clearly pointing to OGs as players in the growth‐defence trade‐off. Here we report a mechanism that may control the homeostasis of OGs avoiding their deleterious hyper‐accumulation. By combining affinity chromatography on acrylamide‐trapped OGs and other procedures, an Arabidopsis thaliana enzyme that specifically oxidizes OGs was purified and identified. The enzyme was named OG OXIDASE 1 (OGOX1) and shown to be encoded by the gene At4g20830. As a typical flavo‐protein, OGOX1 is a sulphite‐sensitive H₂O₂‐producing enzyme that displays maximal activity on OGs with a degree of polymerization >4. OGOX1 belongs to a large gene family of mainly apoplastic putative FAD‐binding proteins [Berberine Bridge Enzyme‐like (BBE‐like); 27 members], whose biochemical and biological function is largely unexplored. We have found that at least four BBE‐like enzymes in Arabidopsis are OG oxidases (OGOX1–4). Oxidized OGs display a reduced capability of activating the immune responses and are less hydrolysable by fungal polygalacturonases. Plants overexpressing OGOX1 are more resistant to Botrytis cinerea, pointing to a crucial role of OGOX enzymes in plant immunity.     

Plant systems for recognition of pathogen-associated molecular patterns

Research of the last decade has revealed that plant immunity consists of different layers of defense that have evolved by the co-evolutional battle of plants with its pathogens. Particular light has been shed on PAMP- (pathogen-associated molecular pattern) triggered immunity (PTI) mediated by pattern recognition receptors. Striking similarities exist between the plant and animal innate immune system that point for a common optimized mechanism that has evolved independently in both kingdoms. Pattern recognition receptors (PRRs) from both kingdoms consist of leucine-rich repeat receptor complexes that allow recognition of invading pathogens at the cell surface. In plants, PRRs like FLS2 and EFR are controlled by a co-receptor SERK3/BAK1, also a leucine-rich repeat receptor that dimerizes with the PRRs to support their function. Pathogens can inject effector proteins into the plant cells to suppress the immune responses initiated after perception of PAMPs by PRRs via inhibition or degradation of the receptors. Plants have acquired the ability to recognize the presence of some of these effector proteins which leads to a quick and hypersensitive response to arrest and terminate pathogen growth.     

Plant pattern-recognition receptors controlling innate immunity

Plants are exposed to numerous potential pathogenic microbes. To counter the threat, plants have evolved diverse patternrecognition receptors(PRRs), which are receptor kinases(RKs) and receptor proteins(RPs) specialized to detect conserved pathogen/microbe-associated molecular patterns(PAMPs/MAMPs). Although only a handful of RKs and RPs are known PRRs,they belong to the receptor-like kinase(RLK) and receptor-like protein(RLP) superfamilies that undergo lineage-specific expansion, suggesting that many of these RLKs and RLPs are potential PRRs. Analyses of existing PRRs have uncovered ligand-induced RLK-RK or RLK-RP oligomerization as a common mechanism for immune activation. PRRs can recruit additional components to form dynamic receptor complexes, which mediate specific cellular responses. Detailed analyses of these components are shedding light on molecular mechanisms underlying the regulation of PRR activity and downstream signaling.     

Erratum to: Plant pattern-recognition receptors controlling innate immunity

Plants are exposed to numerous potential pathogenic microbes. To counter the threat, plants have evolved diverse patternrecognition receptors(PRRs), which are receptor kinases(RKs) and receptor proteins(RPs) specialized to detect conserved pathogen/microbe-associated molecular patterns(PAMPs/MAMPs). Although only a handful of RKs and RPs are known PRRs, they belong to the receptor-like kinase(RLK) and receptor-like protein(RLP) superfamilies that undergo lineage- specific expansion, suggesting that many of these RLKs and RLPs are potential PRRs. Analyses of existing PRRs have uncovered ligand-induced RLK-RK or RLK-RP oligomerization as a common mechanism for immune activation. PRRs can recruit additional components to form dynamic receptor complexes, which mediate specific cellular responses. Detailed analyses of these components are shedding light on molecular mechanisms underlying the regulation of PRR activity and downstream signaling.     

Biased perspectives on formyl peptide receptors

The innate immune system is the first line of defense against pathogenic threats. For the early pathogen recognition and activation of cell protective mechanisms, germline-encoded pattern recognition receptors (PRRs) detect characteristic and evolutionary conserved pathogen-associated molecular patterns (PAMPs). PRRs are therefore key elements in the innate immune response; in addition, they sense danger-associated molecular patterns (DAMPs) that are released by host cell molecules under pathophysiological conditions. Formyl peptide receptors (FPRs) are G-protein-coupled PRRs that respond to a surprisingly broad range of ligands, derived from both pathogens and host cells. Here, we exemplary discuss ligands in order to illustrate the wide pathophysiological relevance of the FPR signaling axis in case of e.g., chronic inflammations and to underscore its potential therapeutic value in the light of “biased agonism”, a modern concept of GPCR (G-protein coupled receptors) activation. These novel insights into the GPCR receptor biochemistry will hopefully (re)stimulate FPR-related research and lead to novel strategies for the urgently needed development of drugs with pharmacologically advantageous characteristics.     

Inflammation-induced DNA damage and damage-induced inflammation: a vicious cycle

Inflammation is the ultimate response to the constant challenges of the immune system by microbes, irritants or injury. The inflammatory cascade initiates with the recognition of microorganism-derived pathogen associated molecular patterns (PAMPs) and host cell-derived damage associated molecular patterns (DAMPs) by the pattern recognition receptors (PRRs). DNA as a molecular PAMP or DAMP is sensed directly or via specific binding proteins to instigate pro-inflammatory response. Some of these DNA binding proteins also participate in canonical DNA repair pathways and recognise damaged DNA to initiate DNA damage response. In this review we aim to capture the essence of the complex interplay between DNA damage response and the pro-inflammatory signalling through representative examples.     

病原菌保守性特征分子及其介导的植物抗病性

每种病原菌都有一些保守的特征性分子,也称病原菌相关分子模式(PAMPs)。植物细胞表面的模式识别受体PRRs通过识别病原菌的PAMPs而激发免疫反应(PTI)。目前,已发现多种PRRs/PAMPs的识别模式,如拟南芥FLS2识别细菌鞭毛蛋白、拟南芥EFR识别细菌延长因子Tu(EF-Tu)、水稻CEBiP/CERK1识别真菌几丁质、水稻抗病蛋白XA21识别白叶枯病菌的硫化蛋白Ax21等。这些识别模式都能激发植物的基础免疫反应以抵抗病原菌的侵染。但是病原菌为了成功侵染寄主植物,也进化出一些致病机制,例如向植物细胞中注入毒性效应蛋白阻断PTI途径,或者产生一种"自我伪装"机制以逃避PRRs的识别。因此,研究者们根据PAMPs的结构特性对PRRs重新改造,以期使植物获得持久、广谱和高效的抗性。综述目前已知的PAMPs分子类型、PRRs/PAMPs的识别机制及改造后的新型PRRs,并分析PTI研究中存在的问题及其发展前景。     

Review of innate and specific immunity in plants and animals

Innate immunity represents a trait common to plants and animals, based on the recognition of pathogen associated molecular patterns (PAMPs) by the host pattern recognition receptors (PRRs). It is generally assumed that a pathogen strain, or race, may have elaborated mechanisms to suppress, or evade, the PAMP-triggered immunity. Once this plan was successful, the colonization would have been counteracted by an adaptive strategy that a plant cultivar must have evolved as a second line of defence. In this co-evolutionary context, adaptive immunity and host resistance (cultivar-pathogen race/strain-specific) has been differently selected, in animals and plants respectively, to face specialized pathogens. Notwithstanding, plant host resistance, based on matching between resistance (R) and avirulence (avr) genes, represents a form of innate immunity, being R proteins similar to PRRs, although able to recognize specific virulence factors (avr proteins) rather than PAMPs. Besides, despite the lack of adaptive immunity preserved plants from autoimmune disorders, inappropriate plant immune responses may occur, producing some side-effects, in terms of fitness costs of induced resistance and autotoxicity. A set of similar defence responses shared from plants and animals, such as defensins, reactive oxygen species (ROS), oxylipins and programmed cell death (PCD) are briefly described.     

New insights into TRP channels: Interaction with pattern recognition receptors

An increasing number of studies have implicated that the activation of innate immune system and inflammatory mechanisms are of importance in the pathogenesis of numerous diseases. The innate immune system is present in almost all multicellular organisms in response to pathogens or tissue injury, which is performed via germ-line encoded pattern-recognition receptors (PRRs) to recognize pathogen-associated molecular patterns (PAMPs) or dangers-associated molecular patterns (DAMPs). Intracellular pathways linking immune and inflammatory response to ion channel expression and function have been recently identified. Among ion channels, transient receptor potential (TRP) channels are a major family of non-selective cation-permeable channels that function as polymodal cellular sensors involved in many physiological and pathological processes. In this review, we summarize current knowledge about classifications, functions, and interactions of TRP channels and PRRs, which may provide new insights into their roles in the pathogenesis of inflammatory diseases.     

线粒体损伤相关模式分子与宿主免疫调节

线粒体是真核细胞至关重要的细胞器,参与机体细胞能量代谢和细胞凋亡等多种生物学过程。线粒体还参与机体的天然免疫反应的调节。线粒体不仅可以作为病毒免疫反应的载体,还可以通过产生ROS参与抗菌反应。线粒体受到损伤、刺激后,可释放mtDNA,TFAM,ROS,ATP,心磷脂和甲酰肽等内容物。这些分子可以作为损伤相关模式分子(damage associated molecular patterns, DAMPs)被模式识别受体识别,从而参与宿主的免疫调节。研究表明,线粒体已成为内源性DAMPs的重要来源,在先天性免疫应答以及疾病进展过程中发挥着重要的作用。本文就线粒体来源的损伤相关模式分子在机体免疫调节中的作用进行综述。     

Self/nonself perception and recognition mechanisms in plants: a comparison of self-incompatibility and innate immunity

Analyses of emerging concepts indicate that parallels exist between self-incompatibility and pathogen recognition. In the case of surveillance of 'nonself', plant immune responses are triggered either by pattern recognition receptors (PRRs) that detect conserved pathogen-associated molecular patterns (PAMPs) or by resistance (R) proteins recognizing isolate-specific pathogen effectors. PAMP detection is an important component of innate immunity in plants and serves as an early warning system for the presence of potential pathogens and activation of plant defense mechanisms. In the Brassicaceae, the recognition of 'self' and self-incompatibility are components of a receptor-ligand based mechanism that utilizes an S receptor kinase (SRK) to perceive and reject 'self'-pollen. SRK is an S-domain receptor-like kinase (RLK), which in turn is part of the RLK family, some members of which represent PRRs involved in the detection of PAMPs. S-domain RLKs also occur in species that do not exhibit self-incompatibility and are up-regulated in response to wounding, PAMPs and pathogen recognition. Although evolution may have driven expansion of certain RLK families to serve roles in particular physiological processes, this may not exclude these receptor types from functioning in different programs. Recent findings on self/nonself recognition are reviewed and conceptual and mechanistic links between microbial recognition and self-incompatibility are discussed.     

BRASSINOSTEROID-SIGNALLING KINASES 7 and 8 associate with the FLS2 immune receptor and are required for flg22-induced PTI responses

Pattern-triggered immunity (PTI) is typically initiated in plants by recognition of pathogen- or damage-associated molecular patterns (PAMP/DAMPs) by cell surface-localized pattern recognition receptors (PRRs). Here, we investigated the role in PTI of Arabidopsis thaliana brassinosteroid-signalling kinases 7 and 8 (BSK7 and BSK8), which are members of the receptor-like cytoplasmic kinase subfamily XII. BSK7 and BSK8 localized to the plant cell periphery and interacted in yeast and in planta with FLS2, but not with other PRRs. Consistent with a role in FLS2 signalling, bsk7 and bsk8 single and bsk7,8 double mutant plants were impaired in several immune responses induced by flg22, but not by other PAMP/DAMPs. These included resistance to Pseudomonas syringae and Botrytis cinerea, reactive oxygen species accumulation, callose deposition at the cell wall, and expression of the defence-related gene PR1, but not activation of MAP kinases and expression of the FRK1 and WRKY29 genes. bsk7, bsk8, and bsk7,8 plants also displayed enhanced susceptibility to P. syringae and B. cinerea. Finally, BSK7 and BSK8 variants mutated in their myristoylation site or in the ATP-binding site failed to complement defective phenotypes of the corresponding mutants, suggesting that localization to the cell periphery and kinase activity are critical for BSK7 and BSK8 functions. Together, these findings demonstrate that BSK7 and BSK8 play a role in PTI initiated by recognition of flg22 by interacting with the FLS2 immune receptor.     

Mitogen-activated protein kinase cascades in plant signaling

Mitogen-activated protein kinase (MAPK) cascades are key signaling modules downstream of receptors/sensors that perceive either endogenously produced stimuli such as peptide ligands and damage-associated molecular patterns (DAMPs) or exogenously originated stimuli such as pathogen/microbe-associated molecular patterns (P/MAMPs), pathogen-derived effectors, and environmental factors. In this review, we provide a historic view of plant MAPK research and summarize recent advances in the establishment of MAPK cascades as essential components in plant immunity, response to environmental stresses, and normal growth and development. Each tier of the MAPK cascades is encoded by a small gene family, and multiple members can function redundantly in an MAPK cascade. Yet, they carry out a diverse array of biological functions in plants. How the signaling specificity is achieved has become an interesting topic of MAPK research. Future investigations into the molecular mechanism(s) underlying the regulation of MAPK activation including the activation kinetics and magnitude in response to a stimulus, the spatiotemporal expression patterns of all the components in the signaling pathway, and functional characterization of novel MAPK substrates are central to our understanding of MAPK functions and signaling specificity in plants.