Leucine-rich repeat-containing PRRs are the largest subfamily, including LRR-RLP and LRR-RLK family members. LRR-RLP/RLKs detect HPs by interacting with shorter ECD co-receptors of the same family to enhance immune signaling (Smakowska-Luzan et al., 2018). BRASSINOSTEROID INSENSITIVE 1 (BRI1)-ASSOCIATED RECEPTOR KINASE 1 (BAK1) is one of the most versatile co-receptors, also known as SOMATIC EMBRYOGENESIS RECEPTOR KINASES 3 (SERK3). It has only five LRRs in its ECD, which are centrally involved in various PTI signaling pathways (Wu et al., 2020). When hemibiotrophic bacteria interact with plants, a well-studied PRR is the LRR-RK FLS2 in most higher plants, which detects a 22-amino acid peptide derived from the N-terminus of bacterial flg22 (Lee et al., 2021). Recognition of flg22 by FLS2 and its co-receptor BAK1 is accompanied by rapid heterodimerization and phosphorylation, which activate plant immunity. To prevent the host immune responses, P. syringae secrete effectors to interfere with immune signals, such as AvrPto, AvrPtoB, HopB1, etc. AvrPto and AvrPtoB interact with FLS2 to prevent the formation of the FLS2-BAK1 complex and the phosphorylation of BIK1 (Gravino et al., 2017; Lei et al., 2020). HopB1 constitutively interacts with FLS2 prior to the activation of flg22. Upon activation, BAK1 is recruited to the FLS2-HopB1 complex. HopB1 cleaves BAK1 and its analogs via genetic transformation or bacterial delivery to inhibit FLS2 signaling and enhance pathogen virulence (Li et al., 2016; Wu et al., 2020). Like FLS2, another extensively studied LRR is the Arabidopsis EFR, which recognizes the N-terminal N-acetylated elongation factor Tu (EF-Tu) peptide of hemibiotrophic bacteria. Upon ligand binding, BAK1 is also recruited by EFR to participate in host immune signaling. Resistance to the hemibiotrophic bacteria P. syringae is activated by recognition of elf18C by EFR-Cf-9 in conjunction with SOBIR1 and BAK (Wu et al., 2019). In addition, rice LRR-RK XA21 can sense tyrosine sulfonate proteins derived from Xanthomonas oryzae to induce effective resistance to Xoo (Wei et al., 2016). These results suggest that under hemibiotrophic bacterial attack, plant LRR-RLKs participate in immune defense and self-development by phosphorylation upon binding to the corresponding co-receptors. Plant RLKs such as FLS2, EFR, and XA21 all belong to the LRR-XII subfamily, which suggests that RLKs of this subfamily may induce immunity by recognizing various protein ligands of hemibiotrophic bacteria. Similar to RLKs, BAK1 is also recruited to the two-component RLP or SOBIR1 complex by ligand recognition by RLP. BAK1 and SOBIR1 can transphosphorylate each other to activate immune signaling pathways. The Arabidopsis RLP23 forms a receptor complex by interacting with SOBIR1. Upon recognizing NLP20, it recruits the co-receptor BAK1 to the complex to enhance the LRR-mediated plant immune response to HPs (Albert et al., 2015; van der Burgh et al., 2019). Several effectors of hemibiotrophic bacteria, fungi, and oomycetes can prevent host LRR-RLP resistance to pathogens by inhibiting NLP-induced cell death, such as suppressor of necrosis 1 (SNE1) from P. infestans (Kelley et al., 2010), Colletotrichum higginsianum effector candidate (ChECs) from C.higginsianum (Kleemann et al., 2012), and MoNLP 1 (Chen et al., 2021), M. oryzae hypothetical effector gene 13 (MoHEG13; Mogga et al., 2016), and suppressors of plant cell death (SPDs) from M. oryzae (Sharpee et al., 2017). Regardless of whether hemibiotrophic bacteria, fungi, or oomycetes infect plants, although the immune response outcomes are different, FLS, EFR, and RLP23 all rely on kinase domain-containing proteins such as BAK1 or SOBIR1 receptor complexes for immune signaling. Different receptor complexes may elicit diverse immune responses by influencing intracellular structural domain phosphorylation and downstream immune signaling. Further studies of the phosphorylation properties of the different receptor complexes may reveal how these receptors are effective against localized HP infection.

During the game between HPs and plants, plant LysM ectodomains induce immune responses by recognizing N-acetylglucosamine molecules, such as fungal chitin oligomers and bacterial peptidoglycan (PGN; McCombe et al., 2022). The LysM family consists of LysM-RLK and LysM-RLP. LysM-RLKs have a LysM outer domain, a single channel transmembrane domain and a cytoplasmic kinase domain. LysM-RLP has only one outer domain connected to the outer membrane by GPI anchors (Buendia et al., 2018). CERK1 is a typical member of the LysM-RLK family consisting of three LysM structural domains. In rice and Arabidopsis, autophosphorylation of specific amino acids in CERK1 regulates chitin-induced immune signals secreted by HPs (Fliegmann et al., 2011; Suzuki et al., 2016; Yu et al., 2021). CERK1 not only recognizes hemibiotrophic fungal chitin, but is also a crucial co-receptor for bacterial PGN. CERK1, together with lysin motif receptor kinase 1 (LYM1) and LYM3, is required for the perception of bacterial PGN and for the development of basal resistance to P. syringae. Studies have also shown that deletion of CERK1 increases susceptibility to hemibiotrophic fungi and bacteria (Giovannoni et al., 2021). In Arabidopsis, LYK5 exhibits a greater affinity for chitin than CERK1. Once LYK5 externally detects chitin, CERK1 forms a dimer and transmits chitin signals to LYK5. Afterward, CERK1 phosphorylates LYK5 and itself in vesicles, which are then internalized (Erwig et al., 2017). LYK4 and AtCERK1 can form a complete complex with LYK5. LYK4 serves as a scaffolding protein or a co-receptor for LYK5, whereas AtCERK1 senses chitin and mediates homodimerization and phosphorylation, all of which promotes chitin triggering signaling (Wan et al., 2012; Cao et al., 2014; Xue et al., 2019). Unlike the chitin-sensing mechanism in Arabidopsis, the rice LysM-RLP CEBiP recognizes chitin and forms a dimer with OsCERK1 to activate plant disease resistance to HP and initiates downstream immune signaling pathways (Hayafune et al., 2014; Desaki et al., 2018; Hu et al., 2021). The results suggest that dimerization of the LysM receptor plays a vital role in ligand detecting, receptor activation, and immune signal transduction during HP infection. Aggregated PGN from hemibiotrophic bacteria is recognized as PAMP by the LysM receptor in Arabidopsis and activates immunity against hemibiotrophic bacteria in plants. Chitin is a major component of fungal cell walls. It plays a crucial molecular role in LysM-mediated host defense responses. Recognition and immune stimulation of chitin secreted by hemibiotrophic fungi in rice or Arabidopsis depend on the LysM-type PRRs OsCEBiP/OsCERK1, LYK4/LYK5, or AtCERK1, respectively. While plants use different sensing systems for bacterial-secreted PGN and fungal-secreted chitin, the chitin sensing system employed by fungi is structurally similar to the carbohydrate portion of bacterial-secreted PGN.

Plant LysM proteins recognize HPs to induce immune responses. HPs have evolved multiple mechanisms to evade plant immune recognition (Wang et al., 2022; Zhao L. et al., 2023). HPs secrete effectors with LysM domains that compete with high affinity for plant LysM receptors. Alternatively, HPs secrete effectors that modify plant LysM receptors to sequester, mask, alter, or prevent the host from degrading pathogen cell walls. These behaviors would regulate plant cytoplasmic signaling, suppress plant immunity, and regulate the transition of HPs from the biotrophic to the necrotrophic stage (Hu et al., 2021; Tian et al., 2022b). The secreted effector protein Slp1 of M. oryzae contains a LysM domain that accumulates at the early stage of infection between fungi and rice cells. This protein disrupts host chitin-triggered immunity by utilizing the LysM structural domain to competitively bind chitin oligosaccharides with CEBiP (Sanchez-Vallet et al., 2013). Similarly, M. oryzae depends not only on LysM Slp1 but also on MoAa91 of M. oryzae. This protein is vital for surface recognition and inhibition of chitin-induced plant immune responses. Further studies shown that MoAa91 competitively binds chitin to the rice immune receptor CEBiP to inhibit chitin-induced plant immune responses (Li et al., 2020). Many HPs-secreted LysM effectors remove chitin oligomers from the host infection site by intermolecular LysM dimerization, or prevent host recognition of chitin by the formation of polymeric precipitates, such as C.higginsianum ChElp1 and ChElp2 (Takahara et al., 2016; Sanchez-Vallet et al., 2020; Tian et al., 2022a). Intermolecular interactions such as homodimerization and phosphorylation demonstrate the significant implications of precisely management of host-pathogen processes, which are also essential for enhancing disease resistance in crops. However, it is unclear whether there are secreted proteins in HPs that more broadly regulate plant defense responses and cell death, potentially mediating the transition from biotrophy to necrotrophy.

Besides PRRs with LRR structures and LysM structures, there is increasing evidence that WAK receptors and lectin receptors play a significant role in plant-microbe interactions. A number of many immune-related WAKs have also been cloned recently. WAKs, a receptor-like kinase required for recognizing oligogalacturonides (OGs), often possess an extracellular EGF-like domain, and are found in both dicots and monocots (Stephens et al., 2022). They can identify pathogens with different lifestyles and regulate HP resistance by modifying host cell walls and regulating hormone fluctuations within host cells. WAKs play a crucial role in plant signaling pathways for immune and abiotic stress responses (Yue et al., 2022). OsWAKs in rice have been discovered to regulate the basic defense against M. oryzae either positively or negatively. Quantitative resistance has been positively affected by OsWAK14, OsWAK91, and OsWAK92, whereas resistance to rice blast has been negatively affected by OsWAK112d. OsWAK91 participates in intercellular signal transduction by generating ROS with possess antibacterial properties (Delteil et al., 2016). AtWAKL10 is thought to enhance plant resistance against P. syringae. Transgenic Arabidopsis lacking WAK exhibits increased susceptibility to P. syringae compared to the wild type (Bot et al., 2019). WAK receptors may regulate host immune resistance by modulating hormone fluctuations during HP infection of different host plants. Overexpression of OsWAK1 and OsWAK25 can enhance host resistance to M. oryzae, and salicylic acid (SA) treatment can up-regulate the expression of OsWAK1 and OsWAK25 genes (Li et al., 2009; Harkenrider et al., 2016). Recently, it was discovered that GmWAK1 relies on the SA pathway to alleviate oxidative stress-induced damage in soybeans resistant to P. infestans (Zhao M. et al., 2023). Immune-related WAK also prevents pathogen penetration during HP attack by altering cell wall composition to enhance cell wall strength. Upon infection of tomato by P. syringae, SlWAK1 strengthens the cell wall through callose deposition to restrict pathogen penetration and spread (Zhang et al., 2020). This ability of WAKs to regulate the cell wall indicates their potential role in plant growth, development, and response to abiotic stresses. OsWAK91/OsDees1 knockout rice has increased susceptibility to M. oryzae and inhibited growth (Delteil et al., 2016). In tomato, AtWAKL10 exhibits resistance to P. syringae while also upregulated when treated with the abiotic stress signaling factor S-nitroso-L-cysteine. Additionally, its knockout gene mutant displays increased tolerance to drought stress, but lower tolerance to salt stress (Bot et al., 2019). The WAK receptors not only enhance or inhibit host resistance when different HPs infect various hosts, but also affect plant growth and development. The mechanisms by which WAK receptors recognize or transduce pathogen signals and their impact on the transition of HPs from the biotrophic to necrotrophic stage remain unclear.

Lectin receptor-like kinases (LecRKs) are unique PRRs that specifically recognize carbohydrates such as mannose induced by elicitors or pathogens (De Coninck and Van Damme, 2022). LecRKs appear to constitute a vital recognition system on the surface of plant cells during plant-microbe interactions, and may play a vital role in plant immunity or stress responses (Wang and Gou, 2022). Furthermore, LecRKs are classified into L-type, C-type, and G-type. G-type and L-type LecRKs are activated by PAMP signaling perception, which triggers PTI to HPs. G-type LecRKs Pi-d2 and OsLecRK have been found to trigger plant defense against rice blast and leaf blight, as well as activate various signal responses in plant innate immunity (Li et al., 2015). Among them, the OsLecRK mutant is more susceptible to Magnaporthe grisea infection than the wild type, with a reduction in mRNA levels of PR1, LOX2, and CHS defense-related genes (Cheng et al., 2013). Similar to LRR receptors, G-type SBP1 and SBP2 can specifically activate immunity by positively regulating the interaction between RLP23 receptors and BAK1 co-receptors (Bao et al., 2023). G-type LecRK LORE was identified as a target site for the effector HopAO1 of P. syringae. During the initial stages of infection, LORE detects bacterial lipopolysaccharides and triggers autophosphorylation to activate the immune response. In the advanced stage of infection, HopAO1 interacts with LORE within host cells, leading to the dephosphorylation of LORE. This effectively suppresses the immune response and makes the host more susceptible to the infection (Chen et al., 2017; Luo et al., 2020). HPs that secrete various molecules recognized by the same host PRR receptors lead to diverse plant immune reactions. Phytohormones play a vital role in plant-pathogen interactions, such as JA, which activate plant defense responses against pathogens. The G-type Lec-RLK FaMBL1 from strawberry can bind to mannose from the cell wall of Colletotrichum fioriniae. Overexpression of FaMBL1 leads to a reduction in JA content (Ma et al., 2023). The L-types of LecRK-IX.1, LecRK-IX.2, and LecRK-I.9 in Arabidopsis are considered to have defense responses against Phytophthora. Overexpression of LecRK-IX.2 phosphorylates RBOHD to enhance ROS production and SA accumulation in PTI response (Wang Y. et al., 2015; Wang Y. et al., 2016; Luo et al., 2017). Similar to LecRK-IX.2, LecRK-I.9 is another L-type LecRK in Arabidopsis, known as DORN1, which also confers plant resistance to P. syringae DC3000 and Phytophthora resistance (Balague et al., 2017; Sun Y. L. et al., 2020). DORN1 recognizes extracellular ATP signals and directly phosphorylates RBOHD. This induces Ca2⁺ influx, MAPK activation, ROS accumulation, and defense gene expression, and host stomatal closure to restrict HPs invasion (Luo et al., 2017; Wang et al., 2018). These studies indicate that LecRLKs are involved in PTI, ETI, SA, and JA signaling pathways and could enhance plant defense against HPs. In molecular breeding, manipulation of one pathway may impact other signaling responses, due to the interconnected nature of these pathways.

Most of the proteins encoded by R genes in each plant genome are NLRs. NLRs directly or indirectly recognize effectors secreted by HPs and activate ETI response (Barragan and Weigel, 2021). Direct interaction between hemibiotrophic effectors and plant NLRs is the most intuitive and simple method. Most CNLs act as effector receptors, called sensor CNL. For example, plant CNLs detect their cognate effectors via direct interactions. Rice NLR Pi-ta binds to the M. oryzae effector AVR-Pita (Jia et al., 2000). Intriguingly, the CNL protein encoded by the Pik allele in rice can also perceive multiple AVR-Pik effectors of M. oryzae via physical interaction. Pikm can recognize three AvrPik effectors of M. oryzae, while Pikp can recognize only one (De la Concepcion et al., 2018).

Hemibiotrophic pathogens are mainly recognized by NLR receptors indirectly. Two recognition models can well describe the indirect interaction between ligands and receptors, namely the “guard” model and the “decoy” model (van der Hoorn and Kamoun, 2008). Modification of guards or decoys by effectors may cause changes in the conformation of NLRs, which leads to the activation of ETI (Schreiber et al., 2016). Since many effectors targeted by NLRs are unknown, and it is often unclear whether these effector targets are guardees or decoys (Kapos et al., 2019). The “guard” model suggests that NLR proteins monitor the integrity of target proteins in plant cells and activate immune responses upon perturbation or modification by pathogen effectors. For example, P. syringae effectors AvrRpm1, AvrB, and AvrRpt2 specifically target the guardee protein RPM1-interacting 4 (RIN4), while CNLs RPM1 and RPS2 monitor RIN4 steric hindrance or post-translational modification to exert disease resistance (Day et al., 2005; El Kasmi et al., 2017). In soybean, CNL RPG1-B monitors the homolog RIN4 in a comparable way (Selote and Kachroo, 2010). Another well-studied example is that of the guardee CNL RPS5 monitors the host target kinase PBS1, where the P. syringae effector protease AvrPphB cleaves PBS1 to activate RPS5-mediated immunity (Ade et al., 2007). It is generally established that all kinases and pseudokinases serve as “guards” or “decoys,” and interact with CNLs, but not with TNLs. Decoy proteins have no defined biological, cellular, or physiological role in host defense. Instead, they imitate toxic targets to activate the host surveillance system and detect effector molecules. Decoys probably evolved by duplicating ancestral guardians (van Wersch et al., 2020). As a decoy protein, the pseudokinase RLCK XII family ZED1 interacts with the acetyltransferase HopZ1a effector secreted by P. syringae. ZED1 is acetylated to activate CNL ZAR1 (Wang G. X. et al., 2015). Recent research revealed that ZED1 forms a complex with ZAR1 after acetylation by HopZ1a, triggering the assembly of higher-order complexes in plants that form a resistosome similar to the ZAR1-RKS1-PBL2^UMP complex (Hu et al., 2020). Other RLCKs are targeted by HopZ1a and are recognized by the ZAR1-ZED1 complex. RKS1 performs an adapter function similar to ZED1 (Bastedo et al., 2019). The pseudokinase ZRK3 and the RLCK family SZE1 and SZE2 also bind to ZAR1 (Liu et al., 2019). It appears that indirect interactions may expand the capacity of certain plant immune receptors to detect additional pathogen effectors. Furthermore, indirect interactions may offer more avenues to enhance pathogen control by regulating receptors.

Plant NLRs’ assembly, activity, and stability are tightly regulated to ensure appropriate host defense responses against HPs. Studies have shown that molecular chaperones and ubiquitin ligases are essential for NLRs’ assembly, activity, and stability (Duxbury et al., 2021; Huang et al., 2021). There are several chaperones in the HSP90 family that play a role in NLR-mediated defenses in Arabidopsis. HSP90.2 interacts with CNL RPM1 to strengthen RPM1 protein stability. HSP90.3 interacts with TNL SNC1 to negatively regulate SNC1 accumulation (Hubert et al., 2003; Huang S. et al., 2014). Recent studies have shown that the P. syringae effector HopBF1 phosphorylates HSP90 to trigger hypersensitivity in plants. This finding uncovers a previously unidentified mechanism by which hemibiotrophic bacteria regulate host immunity (Lopez et al., 2019). And HSP90 may assist the suppressor of G-two allele of SKP1 (SGT1) in forming the Skp1-Cul1-F-box (SCF) E3 ubiquitin ligase complex, which targets immune receptors for degradation. This process is critical for maintaining appropriate levels of immune receptor proteins to avoid autoimmunity. Similarly, ubiquitin ligases interact with NLRs to help regulate their levels without pathogen infection. Upon P. syringae infection, the proteasome effector destroys the E3 ligase F-box protein CPR1, interacts with Arabidopsis TNL SNC1 and CNL RPS2, and reduces their protein accumulation, thus inducing a defense response (Gou et al., 2012). Knocking down the E4 ligase MUSE3 in Arabidopsis causes increased levels of TNL SNC1 and CNL RPS2. Overexpression of MUSE3 and CPR1 enhanced polyubiquitination and protein degradation of these immune receptors (Huang Y. et al., 2014). Host molecular chaperones and ubiquitin indirectly control NLR activity and stability to modulate immune responses when various HP infect the host. This suggests that NLR activity and homeostasis are critical for plant disease resistance.

Transcriptional reprogramming is a frequent occurrence in plant immunity that involves numerous transcriptional regulators. The coordination and nuclear localization of NLRs and immune transcription factors in the transcriptional machinery is crucial to selectively activate plant defense genes during HPs infection. The transcription factor RRM shows CNL-dependent nuclear localization and is unaffected by HPs. RRM binds to the CNL encoded by the resistance genes PigmR, Pi9, and Piz-t, and establishes a direct link between transcriptional activation of the immune response and NLR-mediated pathogen perception by directly binding to the A/T-rich cis-element DNA in the target gene (Zhai et al., 2019). This is in contrast to the nuclear localization of the constitutive transcription factor WRKY45. This transcription factor induces resistance through the SA signaling pathway regulated by the ubiquitin-proteasome system. The CNL protein encoded by the rice blast resistance gene Pb1 interacts with WRKY45 in the nucleus to regulate broad-spectrum resistance to M. oryzae (Inoue et al., 2013). EDS1 regulates the defense signaling pathway. The interactions between Arabidopsis NLR RSP4 and EDS1 result in similar but distinct nuclear NLR-dependent translocations. The RPS4 and EDS1 complex is predominantly located in the cytoplasm, but can also be observed in the nucleus during homeostasis or upon AvrRPS4 infection. Additionally, RPS4 binds to EDS1 in the cytoplasm without relying on another NLR RRS1. Instead, when RRS1 is present, an RPS4-EDS1 complex is observed in the nucleus. This suggests the existence of pre- and post-activation states for the nuclear localization of RPS4, RRS1 and EDS1 complexes. The RPS4-EDS1 binding in the nucleus may be unaffected by HP effectors such as AvrRps4 in the presence of RRS1 (Wang R. Y. et al., 2016). It has also been shown that the effector Avrpiz-t from M. oryzae interacts with the bzip-type transcription factor APIP5 in the cytoplasm, inhibiting its transcriptional activity and protein accumulation during the necrotic stage. Additionally, the rice NLR Piz-t inhibits plant ETI necrosis by interacting with APIP5 (Wang R. Y. et al., 2016). These showing how the host utilizes transcription factors as imitation substances for effectors to prevent host immune responses induced by various HPs.

Many NLRs paired with additional domains or motifs are also critical for plant protection against HPs compared to regular NLRs. The paired NLR contains one NLR with an ID at its C-terminus that mimics the virulence target of an effector protein, and thus acts as a sensor for detecting effector proteins. Another NLR acts as a classical executive NLR that performs signal transduction functions (Grund et al., 2019). Some NLR gene pairs are frequently close in the same locus on the chromosome. These pairs share a promoter. The two genes that encode RPS4 and RRS1 are located adjacent to each other and are arranged in opposite directions. This suggests they may co-regulate transcription, with an interval of approximately 300 bp between them (Narusaka et al., 2009). RRS1 has an extra structural domain called WRKY at the C-terminus. RPS4 and RRSI together form a heterodimeric complex that recognizes the effector AvrRps4 and confers resistance to P. syringae (Guo et al., 2020). In rice, the C-terminus of the NLR-paired RGA5 contains an HMA structural domain that acts as an ID that interacts with the effectors AVR1-CO39 and AVR-Pia in M. oryzae. The NLR-paired RGA4 acts as an NLR executor that induces robust HR in tobacco leaves (Cesari et al., 2013; De la Concepcion et al., 2021). The co-expression of Pikp-1, Pikp-2, and M. oryzae effector AVR-PikD, where Pikp-1 possesses an HMA, and Pikp-2 conducts signal transduction, induces a significant HR in tobacco (Maqbool et al., 2015; Cesari et al., 2022). Guardees or decoys allows plants to detect a wide range of pathogen effectors with a relatively small repertoire of NLRs (Frailie and Innes, 2021; Liu et al., 2021). In the RPS4/RRS1 and RGA4/RGA5 heterodimers, one NLR is involved in effector identification while the other is involved in defense signaling. Understanding the extent of heterodimerization in plant NLRs is crucial in gaining insights into plant NLR evolution and diversity. Moreover, pairing NLR sensors and actuators in plant design could improve effector recognition specificity and resistance profiles.