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Nucleotide-binding, leucine-rich repeat (LRR) proteins (NLRs) are a major class of immune receptors in plants. NLRs include both conserved and rapidly evolving members; however, their evolutionary trajectory in crops remains understudied. Availability of crop pan-genomes enables analysis of the recent events in the evolution of this highly complex gene family within domesticated species. Here, we investigated the NLR complement of 26 nested association mapping (NAM) founder lines of maize. We found that maize has just four main subfamilies containing rapidly evolving highly variable NLR (hvNLR) receptors. Curiously, three of these phylogenetically distinct hvNLR lineages are located in adjacent clusters on chromosome 10. Members of the same hvNLR clade show variable expression and methylation across lines and tissues, which is consistent with their rapid evolution. By combining sequence diversity analysis and AlphaFold2 computational structure prediction, we predicted ligand-binding sites in the hvNLRs. We also observed novel insertion domains in the LRR regions of two hvNLR subfamilies that likely contribute to target recognition. To make this analysis accessible, we created NLRCladeFinder, a Google Colaboratory notebook, that accepts any newly identified NLR sequence, places it in the evolutionary context of the maize pan-NLRome, and provides an updated clade alignment, phylogenetic tree, and sequence diversity information for the gene of interest. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Nucleotide-binding domain leucine-rich repeat (NLR) proteins are a key component of the plant innate immune system. In plant genomes, NLRs exhibit considerable presence/absence variation and sequence diversity. Recent advances in sequencing technologies have made the generation of high-quality novel plant genome assemblies considerably more straightforward. Accurately identifying NLRs from these genomes is a prerequisite for improving our understanding of NLRs and identifying novel sources of disease resistance. While several tools have been developed to predict NLRs, they are hampered by low accuracy, speed, and availability. Here, the NLR annotation tool Resistify is presented. Resistify is an easy-to-use, rapid, and accurate tool to identify and classify NLRs from protein sequences. Applying Resistify to the RefPlantNLR database demonstrates that it can correctly identify NLRs from a diverse range of species. Applying Resistify in combination with tools to identify transposable elements to a panel of Solanaceae genomes reveals a previously undescribed association between NLRs and Helitron transposable elements. [ABSTRACT FROM AUTHOR]

Lathyrus sativus (grass pea) is a valuable crop for sustainable agriculture, offering dietary benefits and desirable agronomic traits. However, its yield stability is limited by diseases such as powdery mildew caused by Erysiphe pisi. Increasing fungal resistance to pesticides and environmental concerns demand the development of resistant crop varieties. To identify key defense mechanisms and effector genes involved in the Lathyrus sativus-Erysiphe pisi interaction we analyzed four L. sativus accessions exhibiting varying resistance to E. pisi (resistant, partially resistant, partially susceptible, and susceptible) using a dual RNA-Seq experiment across different time points. We observed a host biphasic response, characterized by an initial burst of gene expression, followed by a quiescent phase, and a subsequent wave of intense gene expression. Common L. sativus defense mechanisms included antifungal protein expression, cell wall reinforcement, and reactive oxygen species-mediated defense. These defenses involved respectively Bowman-Birk type proteinase inhibitors, peptidyl-prolyl cis-trans isomerases and mannitol dehydrogenases. The resistant accession specifically activated early reinforcement of structural barriers associated with lignin biosynthesis and the phenylpropanoid pathway, along with sustained chemical defenses (e.g. eugenol synthase 1), epigenetic regulation, and oxidative stress responses thorough peroxidases and heat shock proteins. The partial resistant accession exhibited a front-loaded defense response at early infection stages. Contrastingly, the partially susceptible accession exhibited a weaker baseline defense, with a slower and less robust response targeting pathogen infection. We identified potential E. pisi effectors, including genes involved in cell wall hydrolysis (e.g. mannosidase DCW1), nutrient acquisition (e.g. secreted alpha-glucosidase), and virulence (e.g. SnodProt1), with a higher diversity of effectors identified in the susceptible accession. In conclusion, this study identifies novel targets such as NLRs and effectors, antifungal proteins and genes related to cell wall reinforcement, within the complex Lathyrus sativus-Erysiphe pisi interaction to support future breeding programs aimed at enhancing resistance to E. pisi in L. sativus and related species.

IntroductionAlzheimer’s disease (AD), a prevalent neurodegenerative disease, is primarily characterized by progressive neuron loss and memory impairment. NOD-like receptors (NLRs) are crucial for immune regulation and maintaining cellular homeostasis. Recently, NLRs have been identified as important contributors to neuroinflammation, thus presenting a potential approach for reducing inflammation and slowing AD progression.MethodsWe use quantitative RT-PCR to detect levels of NLR family members in AD mouse model. Additionally, we use immunofluorescence to detect NLRP3 expressions in microglia surrounding Aβ plaques in AD mouse model and human AD patients.ResultsIn this study, we examined the expression of NLR family members in the human AD database, and found increased levels of CIITA, NOD1, NLRC5, NLRP1, NLRP3, NLRP7, NLRP10, NLRP12, and NLRP13 in hippocampus tissue in patients with AD, along with increased levels of NOD1, NLRC5, NLRX1, NLRP3, and NLRP7 levels in frontal cortex tissue. Furthermore, through detecting their levels in AD mouse model, we found that NLRP3 levels were significantly increased. Additionally, we found that NLRP3 expressions were mainly elevated in microglia surrounding Aβ plaques in AD mouse model and human AD patients.DiscussionThese findings highlight the potential important role of NLRP3 in AD pathology, offering new therapeutic targets and interventions.

Abstract Unlike animals, plants are unable to move and lack specialized immune cells and circulating antibodies. As a result, they are always threatened by a large number of microbial pathogens and harmful pests that can significantly reduce crop yield worldwide. Therefore, the development of new strategies to control them is essential to mitigate the increasing risk of crops lost to plant diseases. Recent developments in genetic engineering, including efficient gene manipulation and transformation methods, gene editing and synthetic biology, coupled with the understanding of microbial pathogenicity and plant immunity, both at molecular and genomic levels, have enhanced the capabilities to develop disease resistance in plants. This review comprehensively explains the fundamental mechanisms underlying the tug‐of‐war between pathogens and hosts, and provides a detailed overview of different strategies for developing disease resistance in plants. Additionally, it provides a summary of the potential genes that can be employed in resistance breeding for key crops to combat a wide range of potential pathogens and pests, including fungi, oomycetes, bacteria, viruses, nematodes, and insects. Furthermore, this review addresses the limitations associated with these strategies and their possible solutions. Finally, it discusses the future perspectives for producing plants with durable and broad‐spectrum disease resistance.

Plant intracellular nucleotide-binding domain, leucine-rich repeat-containing receptors (NLRs) activate a robust immune response upon detection of pathogen effectors. How NLRs induce downstream immune defense genes remains poorly understood. The Mediator complex plays a central role in transducing signals from gene-specific transcription factors to the transcription machinery for gene transcription/activation. In this study, we demonstrate that MED10b and MED7 of the Mediator complex mediate jasmonate-dependent transcription repression, and coiled-coil NLRs (CNLs) in Solanaceae modulate MED10b/MED7 to activate immunity. Using the tomato CNL Sw-5b, which confers resistance to tospovirus, as a model, we found that the CC domain of Sw-5b directly interacts with MED10b. Knockout/down of MED10b and other subunits including MED7 of the middle module of Mediator activates plant defense against tospovirus. MED10b was found to directly interact with MED7, and MED7 directly interacts with JAZ proteins, which function as transcriptional repressors of jasmonic acid (JA) signaling. MED10b-MED7-JAZ together can strongly repress the expression of JA-responsive genes. The activated Sw-5b CC interferes with the interaction between MED10b and MED7, leading to the activation of JA-dependent defense signaling against tospovirus. Furthermore, we found that CC domains of various other CNLs including helper NLR NRCs from Solanaceae modulate MED10b/MED7 to activate defense against different pathogens. Together, our findings reveal that MED10b/MED7 serve as a previously unknown repressor of jasmonate-dependent transcription repression and are modulated by diverse CNLs in Solanaceae to activate the JA-specific defense pathways.

Many resistance genes deployed against pathogens in crops are intracellular nucleotide-binding (NB) leucine-rich repeat (LRR) receptors (NLRs). The ability to rationally engineer the specificity of NLRs will be crucial in the response to newly emerging crop diseases. Successful attempts to modify NLR recognition have been limited to untargeted approaches or depended on previously available structural information or knowledge of pathogen-effector targets. However, this information is not available for most NLR-effector pairs. Here, we demonstrate the precise prediction and subsequent transfer of residues involved in effector recognition between two closely related NLRs without their experimentally determined structure or detailed knowledge about their pathogen effector targets. By combining phylogenetics, allele diversity analysis, and structural modeling, we successfully predicted residues mediating interaction of Sr50 with its cognate effector AvrSr50 and transferred recognition specificity of Sr50 to the closely related NLR Sr33. We created synthetic versions of Sr33 that contain amino acids from Sr50, including Sr33syn, which gained the ability to recognize AvrSr50 with 12 amino-acid substitutions. Furthermore, we discovered that sites in the LRR domain needed to transfer recognition specificity to Sr33 also influence autoactivity in Sr50. Structural modeling suggests these residues interact with a part of the NB-ARC domain, which we named the NB-ARC latch, to possibly maintain the inactive state of the receptor. Our approach demonstrates rational modifications of NLRs, which could be useful to enhance existing elite crop germplasm. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background Sponges (phylum Porifera) constantly interact with microbes. They graze on microbes from the water column by filter-feeding and they harbor symbiotic partners within their bodies. In experimental setups, sponges take up symbionts at lower rates compared with seawater microbes. This suggests that sponges have the capacity to differentiate between microbes and preferentially graze in non-symbiotic microbes, although the underlying mechanisms of discrimination are still poorly understood. Genomic studies showed that, compared to other animal groups, sponges present an extended repertoire of immune receptors, in particular NLRs, SRCRs, and GPCRs, and a handful of experiments showed that sponges regulate the expression of these receptors upon encounter with microbial elicitors. We hypothesize that sponges may rely on differential expression of their diverse repertoire of poriferan immune receptors to sense different microbial consortia while filter-feeding. To test this, we characterized the transcriptomic response of two sponge species, Aplysina aerophoba and Dysidea avara, upon incubation with microbial consortia extracted from A. aerophoba in comparison with incubation with seawater microbes. The sponges were sampled after 1 h, 3 h, and 5 h for RNA-Seq differential gene expression analysis. Results D. avara incubated with A. aerophoba-symbionts regulated the expression of genes related to immunity, ubiquitination, and signaling. Within the set of differentially-expressed immune genes we identified different families of Nucleotide Oligomerization Domain (NOD)-Like Receptors (NLRs). These results represent the first experimental evidence that different types of NLRs are involved in microbial discrimination in a sponge. In contrast, the transcriptomic response of A. aerophoba to its own symbionts involved comparatively fewer genes and lacked genes encoding for immune receptors. Conclusion Our work suggests that: (i) the transcriptomic response of sponges upon microbial exposure may imply “fine-tuning” of baseline gene expression as a result of their interaction with microbes, (ii) the differential response of sponges to microbial encounters varied between the species, probably due to species-specific characteristics or related to host’s traits, and (iii) immune receptors belonging to different families of NLR-like genes played a role in the differential response to microbes, whether symbionts or food bacteria. The regulation of these receptors in sponges provides further evidence of the potential role of NLRs in invertebrate host-microbe interactions. The study of sponge responses to microbes exemplifies how investigating different animal groups broadens our knowledge of the evolution of immune specificity and symbiosis.

Summary: Plants face a relentless onslaught from a diverse array of pathogens in their natural environment, to which they have evolved a myriad of strategies that unfold across various temporal scales. Cell surface pattern recognition receptors (PRRs) detect conserved elicitors from pathogens or endogenous molecules released during pathogen invasion, initiating the first line of defence in plants, known as pattern‐triggered immunity (PTI), which imparts a baseline level of disease resistance. Inside host cells, pathogen effectors are sensed by the nucleotide‐binding/leucine‐rich repeat (NLR) receptors, which then activate the second line of defence: effector‐triggered immunity (ETI), offering a more potent and enduring defence mechanism. Moreover, PTI and ETI collaborate synergistically to bolster disease resistance and collectively trigger a cascade of downstream defence responses. This article provides a comprehensive review of plant defence responses, offering an overview of the stepwise activation of plant immunity and the interactions between PTI‐ETI synergistic signal transduction. [ABSTRACT FROM AUTHOR]

SUMMARY: Brassica carinata (BBCC) commonly referred to as Ethiopian mustard is a natural allotetraploid containing the genomes of Brassica nigra (BB) and Brassica oleracea (CC). It is an oilseed crop endemic to the northeastern regions of Africa. Although it is under limited cultivation, B. carinata is valuable as it is resistant/highly tolerant to most of the pathogens affecting widely cultivated Brassica species of the U's triangle. We report a chromosome‐scale genome assembly of B. carinata accession HC20 using long‐read Oxford Nanopore sequencing and Bionano optical maps. The assembly has a scaffold N50 of ~39.8 Mb and covers ~1.11 Gb of the genome. We compared the long‐read genome assemblies of the U's triangle species and found extensive gene collinearity between the diploids and allopolyploids with no evidence of major gene losses. Therefore, B. juncea (AABB), B. napus (AACC), and B. carinata can be regarded as strict allopolyploids. We cataloged the nucleotide‐binding and leucine‐rich repeat immune receptor (NLR) repertoire of B. carinata and, identified 465 NLRs, and compared these with the NLRs in the other Brassica species. We investigated the extent and nature of early‐generation genomic interactions between the constituent genomes of B. carinata and B. juncea in interspecific crosses between the two species. Besides the expected recombination between the constituent B genomes, extensive homoeologous exchanges were observed between the A and C genomes. Interspecific crosses, therefore, can be used for transferring disease resistance from B. carinata to B. juncea and broadening the genetic base of the two allotetraploid species. Significance Statement: We report a highly contiguous genome assembly of allotetraploid mustard Brassica carinata HC20 (BBCC) which contains resistance to many diseases affecting the other extensively cultivated Brassica species of the U's triangle. Comparative analyses of the long‐read assemblies of the six Brassica species revealed high gene collinearity between the three diploid and their allotetraploid species. We tracked the early‐generation genomic interactions between the subgenomes of B. carinata (BBCC) and B. juncea (AABB) in their interspecific crosses using molecular karyotyping and proposed strategies to utilize this information for genomic introgressions. [ABSTRACT FROM AUTHOR]

Background: Sponges (phylum Porifera) constantly interact with microbes. They graze on microbes from the water column by filter-feeding and they harbor symbiotic partners within their bodies. In experimental setups, sponges take up symbionts at lower rates compared with seawater microbes. This suggests that sponges have the capacity to differentiate between microbes and preferentially graze in non-symbiotic microbes, although the underlying mechanisms of discrimination are still poorly understood. Genomic studies showed that, compared to other animal groups, sponges present an extended repertoire of immune receptors, in particular NLRs, SRCRs, and GPCRs, and a handful of experiments showed that sponges regulate the expression of these receptors upon encounter with microbial elicitors. We hypothesize that sponges may rely on differential expression of their diverse repertoire of poriferan immune receptors to sense different microbial consortia while filter-feeding. To test this, we characterized the transcriptomic response of two sponge species, Aplysina aerophoba and Dysidea avara, upon incubation with microbial consortia extracted from A. aerophoba in comparison with incubation with seawater microbes. The sponges were sampled after 1 h, 3 h, and 5 h for RNA-Seq differential gene expression analysis. Results: D. avara incubated with A. aerophoba-symbionts regulated the expression of genes related to immunity, ubiquitination, and signaling. Within the set of differentially-expressed immune genes we identified different families of Nucleotide Oligomerization Domain (NOD)-Like Receptors (NLRs). These results represent the first experimental evidence that different types of NLRs are involved in microbial discrimination in a sponge. In contrast, the transcriptomic response of A. aerophoba to its own symbionts involved comparatively fewer genes and lacked genes encoding for immune receptors. Conclusion: Our work suggests that: (i) the transcriptomic response of sponges upon microbial exposure may imply "fine-tuning" of baseline gene expression as a result of their interaction with microbes, (ii) the differential response of sponges to microbial encounters varied between the species, probably due to species-specific characteristics or related to host's traits, and (iii) immune receptors belonging to different families of NLR-like genes played a role in the differential response to microbes, whether symbionts or food bacteria. The regulation of these receptors in sponges provides further evidence of the potential role of NLRs in invertebrate host-microbe interactions. The study of sponge responses to microbes exemplifies how investigating different animal groups broadens our knowledge of the evolution of immune specificity and symbiosis. [ABSTRACT FROM AUTHOR]

In plants, nucleotide-binding site and leucine-rich repeat proteins (NLRs) play pivotal roles in effector-triggered immunity (ETI). However, the precise mechanisms underlying NLR-mediated disease resistance remain elusive. Previous studies have demonstrated that the NLR gene pair Pik-H4 confers resistance to rice blast disease by interacting with the transcription factor OsBIHD1, consequently leading to the upregulation of hormone pathways. In the present study, we identified an RNA recognition motif (RRM) protein, OsRRM2, which interacted with Pik1-H4 and Pik2-H4 in vesicles and chloroplasts. OsRRM2 exhibited a modest influence on Pik-H4-mediated rice blast resistance by upregulating resistance genes and genes associated with chloroplast immunity. Moreover, the RNA-binding sequence of OsRRM2 was elucidated using systematic evolution of ligands by exponential enrichment. Transcriptome analysis further indicated that OsRRM2 promoted RNA editing of the chloroplastic gene ndhB. Collectively, our findings uncovered a chloroplastic RRM protein that facilitated the translocation of the NLR gene pair and modulated chloroplast immunity, thereby bridging the gap between ETI and chloroplast immunity. [ABSTRACT FROM AUTHOR]

Knowledge of plant recognition of insects is largely limited to a few resistance (R) genes against sap‐sucking insects. Hypersensitive response (HR) characterizes monogenic plant traits relying on R genes in several pathosystems. HR‐like cell death can be triggered by eggs of cabbage white butterflies (Pieris spp.), pests of cabbage crops (Brassica spp.), reducing egg survival and representing an effective plant resistance trait before feeding damage occurs. Here, we performed genetic mapping of HR‐like cell death induced by Pieris brassicae eggs in the black mustard Brassica nigra (B. nigra). We show that HR‐like cell death segregates as a Mendelian trait and identified a single dominant locus on chromosome B3, named PEK (Pieris egg‐ killing). Eleven genes are located in an approximately 50 kb region, including a cluster of genes encoding intracellular TIR‐NBS‐LRR (TNL) receptor proteins. The PEK locus is highly polymorphic between the parental accessions of our mapping populations and among B. nigra reference genomes. Our study is the first one to identify a single locus potentially involved in HR‐like cell death induced by insect eggs in B. nigra. Further fine‐mapping, comparative genomics and validation of the PEK locus will shed light on the role of these TNL receptors in egg‐killing HR. Summary statement: Hypersensitive response induced by cabbage white butterfly eggs in Brassica spp. reduces survival and represents an effective plant resistance trait. For the first time, a single dominant locus was identified in the wild crucifer Brassica nigra, which contains a cluster of genes encoding intracellular TIR‐NBS‐LRR (TNLs) receptors. [ABSTRACT FROM AUTHOR]

SUMMARY: Sorghum anthracnose caused by the fungus Colletotrichum sublineola (Cs) is a damaging disease of the crop. Here, we describe the identification of ANTHRACNOSE RESISTANCE GENES (ARG4 and ARG5) encoding canonical nucleotide‐binding leucine‐rich repeat (NLR) receptors. ARG4 and ARG5 are dominant resistance genes identified in the sorghum lines SAP135 and P9830, respectively, that show broad‐spectrum resistance to Cs. Independent genetic studies using populations generated by crossing SAP135 and P9830 with TAM428, fine mapping using molecular markers, comparative genomics and gene expression studies determined that ARG4 and ARG5 are resistance genes against Cs strains. Interestingly, ARG4 and ARG5 are both located within clusters of duplicate NLR genes at linked loci separated by ~1 Mb genomic region. SAP135 and P9830 each carry only one of the ARG genes while having the recessive allele at the second locus. Only two copies of the ARG5 candidate genes were present in the resistant P9830 line while five non‐functional copies were identified in the susceptible line. The resistant parents and their recombinant inbred lines carrying either ARG4 or ARG5 are resistant to strains Csgl1 and Csgrg suggesting that these genes have overlapping specificities. The role of ARG4 and ARG5 in resistance was validated through sorghum lines carrying independent recessive alleles that show increased susceptibility. ARG4 and ARG5 are located within complex loci displaying interesting haplotype structures and copy number variation that may have resulted from duplication. Overall, the identification of anthracnose resistance genes with unique haplotype stucture provides a foundation for genetic studies and resistance breeding. Significance Statement: We identified two tightly linked NLR genes conferring resistance to the sorghum anthracnose disease that is a major challenge to production of the crop globally. The two genes were identified among clusters of highly similar duplicate genes with resistant and susceptible lines having unique haplotypes, and amino acid substitutions in key positions, leading to changes in tertiary protein structure and disease resistance function. The results provide new opportunities for resistance breeding and genetic and molecular studies. [ABSTRACT FROM AUTHOR]

Abstract Plants have evolved a multilayered and sophisticated immune system to establish effective resistance to a variety of pathogens. Phytophthora species are among the most notorious plant pathogens, causing destructive diseases on a variety of agricultural crops. Understanding the plant immune system is crucial for protecting crops from Phytophthora diseases. Here, we summarize the recent work on genes involved in plant resistance against Phytophthora pathogens, including cell surface pattern recognition receptors, cytoplasmic nucleotide-binding leucine-rich repeat receptors, regulator genes, and non-host resistance genes, small RNA, and long non-coding RNA are also discussed in this review. Although the molecular mechanisms of only a small proportion of them have been clarified, emergence of new mechanisms of plant defense will offer exciting opportunities for utilization of these genes in disease resistance breeding as well as generation of disease-resistant crop germplasms.

Plants have evolved a multilayered and sophisticated immune system to establish effective resistance to a variety of pathogens. Phytophthora species are among the most notorious plant pathogens, causing destructive diseases on a variety of agricultural crops. Understanding the plant immune system is crucial for protecting crops from Phytophthora diseases. Here, we summarize the recent work on genes involved in plant resistance against Phytophthora pathogens, including cell surface pattern recognition receptors, cytoplasmic nucleotide-binding leucine-rich repeat receptors, regulator genes, and non-host resistance genes, small RNA, and long non-coding RNA are also discussed in this review. Although the molecular mechanisms of only a small proportion of them have been clarified, emergence of new mechanisms of plant defense will offer exciting opportunities for utilization of these genes in disease resistance breeding as well as generation of disease-resistant crop germplasms. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM), characterized by production and accumulation of advanced glycation end products (AGEs), induces and promotes chronic inflammation in tissues, including periodontal tissue. Increasing amount of epidemiological and experimental evidence demonstrated that more extensive inflammatory reaction and bone resorption occurred in periodontal tissues in diabetic patients with periodontitis, which is speculated to be related to NLRP3 inflammasome. NLRP10 is the only NOD-like receptor protein lacking leucine-rich repeats, suggesting that NLRP10 may be a regulatory protein. The aim of this study was to investigate the regulatory role of NLRP10 on NLRP1 and NLRP3 inflammasome in human periodontal ligament cells (HPDLCs) under AGEs treatment. Expression of NLRP10 in HPDLCs stimulated with 100 ug/mL AGEs for 24 h was observed. Detection of TRIM31 is conducted, and in TRIM31-overexpressed HPDLCs, the interaction between NLRP10 with TRIM31 as well as NLRP10 with ubiquitination were explored by immunoprecipitation. Under AGEs stimulation, the activation of reactive oxidative stress (ROS) and inflammatory signaling pathway (NF-κB, MAPK pathway) was detected by biomedical microscope and western blot (WB), respectively. After stimulation with AGEs for 24 h with or without silencing NLRP10, inflammatory cytokines (IL-6 and IL-1β), NF-κB, MAPK pathway, ROS, and components of inflammasome were assessed. In HPDLCs, we found AGEs induced NLRP10 and inhibited TRIM31. TRIM31 overexpression significantly enhanced interaction between TRIM31 and NLRP10, then induced proteasomal degradation of NLRP10. Moreover, under AGEs stimulation, NLRP10 positively regulates NLRP1, NLRP3 inflammasomes by activating NF-κB, MAPK pathway, and increasing ROS, finally promoting the expression of inflammatory cytokines. Together, we, for the first time, confirmed that NLRP10 could promote inflammatory response induced by AGEs in HPDLCs via activation of NF-κB, and MAPK pathway and increasing ROS. [ABSTRACT FROM AUTHOR]

Many resistance genes deployed against pathogens in crops are intracellular nucleotide-binding (NB) leucine-rich repeat (LRR) receptors (NLRs). The ability to rationally engineer the specificity of NLRs will be crucial in the response to newly emerging crop diseases. Successful attempts to modify NLR recognition have been limited to untargeted approaches or depended on previously available structural information or knowledge of pathogen-effector targets. However, this information is not available for most NLR-effector pairs. Here, we demonstrate the precise prediction and subsequent transfer of residues involved in effector recognition between two closely related NLRs without their experimentally determined structure or detailed knowledge about their pathogen effector targets. By combining phylogenetics, allele diversity analysis, and structural modeling, we successfully predicted residues mediating interaction of Sr50 with its cognate effector AvrSr50 and transferred recognition specificity of Sr50 to the closely related NLR Sr33. We created synthetic versions of Sr33 that contain amino acids from Sr50, including Sr33syn, which gained the ability to recognize AvrSr50 with 12 amino-acid substitutions. Furthermore, we discovered that sites in the LRR domain needed to transfer recognition specificity to Sr33 also influence autoactivity in Sr50. Structural modeling suggests these residues interact with a part of the NB-ARC domain, which we named the NB-ARC latch, to possibly maintain the inactive state of the receptor. Our approach demonstrates rational modifications of NLRs, which could be useful to enhance existing elite crop germplasm. [Graphic: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Plants possess an arsenal of immune receptors to allow for numerous tiers of defense against pathogen attack. These immune receptors can be located either in the nucleocytoplasm or on the plant cell surface. NLR gene clusters have recently gained momentum owing to their robustness and malleability in adapting to recognize pathogens. The modular domain architecture of an NLR provides valuable clues about its arms race with pathogens. Additionally, plant NLRs have undergone functional specialization to have either one of the following roles: to sense pathogen effectors (sensor NLRs) or co-ordinate immune signaling (helper or executer NLRs). Sensor NLRs directly recognize effectors whilst helper NLRs act as signaling hubs for more than one sensor NLR to transduce the effector recognition into a successful plant immune response. Furthermore, sensor NLRs can use guard, decoy, or integrated decoy models to recognize effectors directly or indirectly. Thus, by studying a plant host's NLR repertoire, inferences can be made about a host's evolutionary history and defense potential which allows scientists to understand and exploit the molecular basis of resistance in a plant host. This review provides a snapshot of the structural and biochemical properties of the different classes of NLRs which allow them to perceive pathogen effectors and contextualize these findings by discussing the activation mechanisms of these NLR resistosomes during plant defense. We also summarize future directives on applications of this NLR structural biology. To our knowledge, this review is the first to collate all vast defense properties of NLRs which make them valuable candidates for study in applied plant biotechnology. [ABSTRACT FROM AUTHOR]

Plants possess an arsenal of immune receptors to allow for numerous tiers of defense against pathogen attack. These immune receptors can be located either in the nucleocytoplasm or on the plant cell surface. NLR gene clusters have recently gained momentum owing to their robustness and malleability in adapting to recognize pathogens. The modular domain architecture of an NLR provides valuable clues about its arms race with pathogens. Additionally, plant NLRs have undergone functional specialization to have either one of the following roles: to sense pathogen effectors (sensor NLRs) or co-ordinate immune signaling (helper or executer NLRs). Sensor NLRs directly recognize effectors whilst helper NLRs act as signaling hubs for more than one sensor NLR to transduce the effector recognition into a successful plant immune response. Furthermore, sensor NLRs can use guard, decoy, or integrated decoy models to recognize effectors directly or indirectly. Thus, by studying a plant host’s NLR repertoire, inferences can be made about a host’s evolutionary history and defense potential which allows scientists to understand and exploit the molecular basis of resistance in a plant host. This review provides a snapshot of the structural and biochemical properties of the different classes of NLRs which allow them to perceive pathogen effectors and contextualize these findings by discussing the activation mechanisms of these NLR resistosomes during plant defense. We also summarize future directives on applications of this NLR structural biology. To our knowledge, this review is the first to collate all vast defense properties of NLRs which make them valuable candidates for study in applied plant biotechnology.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease that involves host genetics, the microbiome, and inflammatory responses. The current consensus is that the disruption of the intestinal mucosal barrier is the core pathogenesis of IBD, including intestinal microbial factors, abnormal immune responses, and impaired intestinal mucosal barrier. Cumulative data show that nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are dominant mediators in maintaining the homeostasis of the intestinal mucosal barrier, which play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Blocking NLRs inflammasome activation by botanicals may be a promising way to prevent IBD progression. In this review, we systematically introduce the multiple roles of NLRs in regulating intestinal mucosal barrier homeostasis and focus on summarizing the activities and potential mechanisms of natural products against IBD. Aiming to propose new directions on the pathogenesis and precise treatment of IBD [ABSTRACT FROM AUTHOR]

Red blood cells (RBCs) are the most abundant cell types in the circulatory system of vertebrates. In fish, RBCs retain their nuclei throughout their lifetime and remain transcriptionally and translationally active. While their primary function is typically associated with gas exchange, recent reports indicate that nucleated red blood cells can play a significant role in regulating the body's innate immune response. The current article describes the innate immune role of red blood cells in rohu (Labeo rohita), a freshwater fish species that holds significant commercial importance in India and South‐East Asian nations. From the whole blood and mucosal surface RBCs have been isolated through density gradient centrifugation with HiSep™LSM 1077 (density 1.007 ± 0.0010) and their purity has been confirmed by the Giemsa staining followed by microscopical observations. Toll‐like receptors (TLR2, 3, 4, 5) and nucleotide oligomerization domain (NOD)‐like receptors (NOD1 and NOD2) in RBCs of rohu fingerlings were observed to be significantly activated (P < 0.05) on infection with Aeromonas hydrophila and Edwardsiella tarda. This activation resulted in increased expression of interleukins (IL‐8, IL‐1β) and interferon (IFN)‐I genes. The activation of TLR4, NOD1 and NOD2, as well as the expression of interleukins and IFN‐I genes have been observed in both in vivo and in vitro stimulation of rohu RBCs with lipopolysaccharides. These findings highlight the importance of fish RBCs in enhancing innate immunity against various pathogenic invasions in rohu. [ABSTRACT FROM AUTHOR]

Plant intracellular nucleotide- binding domain, leucine-rich repeat- containing recep- tors (NLRs) activate a robust immune response upon detection of pathogen effectors. How NLRs induce downstream immune defense genes remains poorly understood. The Mediator complex plays a central role in transducing signals from gene-specific transcription factors to the transcription machinery for gene transcription/activation. In this study, we demonstrate that MED10b and MED7 of the Mediator complex mediate jasmonate-dependent transcription repression, and coiled-coil NLRs (CNLs) in Solanaceae modulate MED10b/MED7 to activate immunity. Using the tomato CNL Sw-5b, which confers resistance to tospovirus, as a model, we found that the CC domain of Sw-5b directly interacts with MED10b. Knockout/down of MED10b and other subunits including MED7 of the middle module of Mediator activates plant defense against tospovirus. MED10b was found to directly interact with MED7, and MED7 directly interacts with JAZ proteins, which function as transcriptional repressors of jasmonic acid (JA) signaling. MED10b–MED7–JAZ together can strongly repress the expression of JA-responsive genes. The activated Sw-5b CC interferes with the interac- tion between MED10b and MED7, leading to the activation of JA-dependent defense signaling against tospovirus. Furthermore, we found that CC domains of various other CNLs including helper NLR NRCs from Solanaceae modulate MED10b/MED7 to activate defense against different pathogens. Together, our findings reveal that MED10b/ MED7 serve as a previously unknown repressor of jasmonate-dependent transcription repression and are modulated by diverse CNLs in Solanaceae to activate the JA-specific defense pathways. [ABSTRACT FROM AUTHOR]

The ever‐growing world population, increasingly frequent extreme weather events and conditions, emergence of novel devastating crop pathogens and the social strive for quality food products represent a huge challenge for current and future agricultural production systems. To address these challenges and find realistic solutions, it is becoming more important by the day to understand the complex interactions between plants and the environment, mainly the associated organisms, but in particular pathogens. In the past several years, research in the fields of plant pathology and plant–microbe interactions has enabled tremendous progress in understanding how certain receptor‐based plant innate immune systems function to successfully prevent infections and diseases. In this review, we highlight and discuss some of these new ground‐breaking discoveries and point out strategies of how pathogens counteract the function of important core convergence hubs of the plant immune system. For practical reasons, we specifically place emphasis on potential applications that can be detracted by such discoveries and what challenges the future of agriculture has to face, but also how these challenges could be tackled. [ABSTRACT FROM AUTHOR]

Modern plant pathology relies on bioinformatics approaches to create novel plant disease diagnostic tools. In recent years, a significant amount of biological data has been generated due to rapid developments in genomics and molecular biology techniques. The progress in the sequencing of agriculturally important crops has made it possible to develop a better understanding of plant–pathogen interactions and plant resistance. The availability of host–pathogen genome data offers effective assistance in retrieving, annotating, analyzing, and identifying the functional aspects for characterization at the gene and genome levels. Physical mapping facilitates the identification and isolation of several candidate resistance (R) genes from diverse plant species. A large number of genetic variations, such as disease-causing mutations in the genome, have been identified and characterized using bioinformatics tools, and these desirable mutations were exploited to develop disease resistance. Moreover, crop genome editing tools, namely the CRISPR (clustered regulatory interspaced short palindromic repeats)/Cas9 (CRISPR-associated) system, offer novel and efficient strategies for developing durable resistance. This review paper describes some aspects concerning the databases, tools, and techniques used to characterize resistance (R) genes for plant disease management. [ABSTRACT FROM AUTHOR]

Background: In the ten years since the initial publication of the RenSeq protocol, the method has proved to be a powerful tool for studying disease resistance in plants and providing target genes for breeding programmes. Since the initial publication of the methodology, it has continued to be developed as new technologies have become available and the increased availability of computing power has made new bioinformatic approaches possible. Most recently, this has included the development of a k-mer based association genetics approach, the use of PacBio HiFi data, and graphical genotyping with diagnostic RenSeq. However, there is not yet a unified workflow available and researchers must instead configure approaches from various sources themselves. This makes reproducibility and version control a challenge and limits the ability to perform these analyses to those with bioinformatics expertise. Results: Here we present HISS, consisting of three workflows which take a user from raw RenSeq reads to the identification of candidates for disease resistance genes. These workflows conduct the assembly of enriched HiFi reads from an accession with the resistance phenotype of interest. A panel of accessions both possessing and lacking the resistance are then used in an association genetics approach (AgRenSeq) to identify contigs positively associated with the resistance phenotype. Candidate genes are then identified on these contigs and assessed for their presence or absence in the panel with a graphical genotyping approach that uses dRenSeq. These workflows are implemented via Snakemake, a python-based workflow manager. Software dependencies are either shipped with the release or handled with conda. All code is freely available and is distributed under the GNU GPL-3.0 license. Conclusions: HISS provides a user-friendly, portable, and easily customised approach for identifying novel disease resistance genes in plants. It is easily installed with all dependencies handled internally or shipped with the release and represents a significant improvement in the ease of use of these bioinformatics analyses. [ABSTRACT FROM AUTHOR]

Plants have evolved two layers of protection against biotic stress: PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI). The primary mechanism of ETI involves nucleotide-binding leucine-rich repeat immune receptors (NLRs). Although NLR genes have been studied in several plant species, a comprehensive database of NLRs across a diverse array of species is still lacking. Here, we present a thorough analysis of NLR genes across 100 high-quality plant genomes (PlantNLRatlas). The PlantNLRatlas includes a total of 68,452 NLRs, of which 3,689 are full-length and 64,763 are partial-length NLRs. The majority of NLR groups were phyletically clustered. In addition, the domain sequences were found to be highly conserved within each NLR group. Our PlantNLRatlas dataset is complementary to RefPlantNLR, a collection of NLR genes which have been experimentally confirmed. The PlantNLRatlas should prove helpful for comparative investigations of NLRs across a range of plant groups, including understudied taxa. Finally, the PlantNLRatlas resource is intended to help the field move past a monolithic understanding of NLR structure and function. [ABSTRACT FROM AUTHOR]

Endometriosis is closely associated with ectopic focal inflammation and immunosuppressive microenvironment. Multiple types of pattern recognition receptors (PRRs) are present in the innate immune system, which are able to detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in both intracellular and external environments. However, the exact role of PRRs in endometriosis and the underlying molecular mechanism are unclear. PRRs are necessary for the innate immune system to identify and destroy invasive foreign infectious agents. Mammals mainly have two types of microbial recognition systems. The first one consists of the membrane)bound receptors, such as toll-like receptors (TLRs), which recognize extracellular microorganisms and activate intracellular signals to stimulate immune responses. The second one consists of the intracellular PRRs, including nod-like receptors (NLRs) and antiviral proteins retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA-5) with helix enzyme domain. In this review, we mainly focus on the key role of PRRs in the pathological processes associated with endometriosis. PRRs recognize PAMPs and can distinguish pathogenic microorganisms from self, triggering receptor ligand reaction followed by the stimulation of host immune response. Activated immune response promotes the transmission of microbial infection signals to the cells. As endometriosis is characterized by dysregulated inflammation and immune response, PRRs may potentially be involved in the activation of endometriosis)associated inflammation and immune disorders. Toll-like receptor 2 (TLR2), toll)like receptor 3 (TLR3), toll-like receptor 4 (TLR4), nod-like receptor family caspase activation and recruitment domain (CARD) domain containing 5 (NLRC5), nod-like receptor family pyrin domain containing 3 (NLRP3), and c-type lectin receptors (CLRs) play essential roles in endometriosis development by regulating immune and inflammatory responses. Absent in melanoma 2 (AIM2)-like receptors (ALRs) and retinoic acid-inducible gene I-like receptors (RLRs) may be involved in the activation of endometriosis-associated immune and inflammation disorders. PRRs, especially TLRs, may serve as potential therapeutic targets for alleviating pain in endometriosis patients. PRRs and their ligands interact with the innate immune system to enhance inflammation in the stromal cells during endometriosis. Thus, targeting PRRs and their new synthetic ligands may provide new therapeutic options for treating endometriosis. [ABSTRACT FROM AUTHOR]

Carica papaya maintains an abnormally small but complete NLR family while showing weak disease resistance. To better understand their origin, evolution, and biological function, we identified 59 NLR genes via a customized RGAugury and investigated their characteristics, evolutionary history, and expression profiles based on the improved papaya genome and large-scale RNA-seq data. The results indicated that duplication is a major evolutionary force driving the formation of the papaya NLR family. Synteny analyses of papaya and other angiosperms showed that both insertion and inheritance-derived NLRs are present in papaya. Transcriptome-based expression and network analyses revealed that NLRs are actively involved in biotic stress responses. For example, a papaya-specific inserted TNL was up-regulated strongly by the fungal infection. Both transcriptome and qRT-PCR analyses confirmed the expression divergence of an RNL and an RCNL, a pair of tandem duplication genes involved in different co-expression modules. Furthermore, we observed an inserted gene cluster composed of five duplicated CNLs, showing dosage effects and functional differentiation of disease-resistance genes during evolution. This research will enhance our knowledge of the special NLR family in papaya, which may serve as a model plant for disease-resistance genetic studies. [ABSTRACT FROM AUTHOR]

Ksenia Krasileva is an Assistant Professor at UC Berkley, studying innate immunity in plants. Ksenia's work combines plant genomics and plant-microbe interactions with new technologies, spanning basic studies and translational research in agriculture. In this interview Ksenia shares her experience with research and leading a lab, as well as thoughts on innovations in publishing.

BackgroundThe plant immune system is innate and encoded in the germline. Using it efficiently, plants are capable of recognizing a diverse range of rapidly evolving pathogens. A recently described phenomenon shows that plant immune receptors are able to recognize pathogen effectors through the acquisition of exogenous protein domains from other plant genes.ResultsWe show that plant immune receptors with integrated domains are distributed unevenly across their phylogeny in grasses. Using phylogenetic analysis, we uncover a major integration clade, whose members underwent repeated independent integration events producing diverse fusions. This clade is ancestral in grasses with members often found on syntenic chromosomes. Analyses of these fusion events reveals that homologous receptors can be fused to diverse domains. Furthermore, we discover a 43 amino acid long motif associated with this dominant integration clade which is located immediately upstream of the fusion site. Sequence analysis reveals that DNA transposition and/or ectopic recombination are the most likely mechanisms of formation for nucleotide binding leucine rich repeat proteins with integrated domains.ConclusionsThe identification of this subclass of plant immune receptors that is naturally adapted to new domain integration will inform biotechnological approaches for generating synthetic receptors with novel pathogen "baits."

SUMMARY: Plant immunity largely relies on intracellular nucleotide‐binding domain leucine‐rich repeat (NLR) immune receptors. Some plant NLRs carry integrated domains (IDs) that mimic authentic pathogen effector targets. We report here the identification of a genetically linked NLR‐ID/NLR pair: BnRPR1 and BnRPR2 in Brassica napus. The NLR‐ID carries two ID fusions and the mode of action of the pair conforms to the proposed "integrated sensor/decoy" model. The two NLRs interact and the heterocomplex localizes in the plant‐cell nucleus and nucleolus. However, the BnRPRs pair does not operate through a negative regulation as it was previously reported for other NLR‐IDs. Cell death is induced only upon co‐expression of the two proteins and is dependent on the helper genes, EDS1 and NRG1. The nuclear localization of both proteins seems to be essential for cell death activation, while the IDs of BnRPR1 are dispensable for this purpose. In summary, we describe a new pair of NLR‐IDs with interesting features in relation to its regulation and the cell death activation. [ABSTRACT FROM AUTHOR]

SUMMARY: Sorghum is an important food and feed crop globally; its production is hampered by anthracnose disease caused by the fungal pathogen Colletotrichum sublineola (Cs). Here, we report identification and characterization of ANTHRACNOSE RESISTANCE GENE 2 (ARG2) encoding a nucleotide‐binding leucine‐rich repeat (NLR) protein that confers race‐specific resistance to Cs strains. ARG2 is one of a cluster of several NLR genes initially identified in the sorghum differential line SC328C that is resistant to some Cs strains. This cluster shows structural and copy number variations in different sorghum genotypes. Different sorghum lines carrying independent ARG2 alleles provided the genetic validation for the identity of the ARG2 gene. ARG2 expression is induced by Cs, and chitin induces ARG2 expression in resistant but not in susceptible lines. ARG2‐mediated resistance is accompanied by higher expression of defense and secondary metabolite genes at early stages of infection, and anthocyanin and zeatin metabolisms are upregulated in resistant plants. Interestingly, ARG2 localizes to the plasma membrane when transiently expressed in Nicotiana benthamiana. Importantly, ARG2 plants produced higher shoot dry matter than near‐isogenic lines carrying the susceptible allele suggesting an absence of an ARG2 associated growth trade‐off. Furthermore, ARG2‐mediated resistance is stable at a wide range of temperatures. Our observations open avenues for resistance breeding and for dissecting mechanisms of resistance. Significance Statement: Sorghum is a crop of global importance that is used for food, feed and biofuel. The crop feeds millions of people, especially small holder framers around the world. The productivity of sorghum is constrained by anthracnose diseases caused by the fungus Colletotrichum sublineola. Genetic resistance provides the most sustainable disease control method. We identified and characterized a sorghum anthracnose resistance gene encoding a nucleotide‐binding leucine‐rich repeat protein by exploring natural variation in the crop. Our findings will have significant implications for improvement of disease resistance in sorghum, as well as for future studies in the molecular genetics of pathogen resistance. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic gastrointestinal inflammatory disease that involves host genetics, the microbiome, and inflammatory responses. The current consensus is that the disruption of the intestinal mucosal barrier is the core pathogenesis of IBD, including intestinal microbial factors, abnormal immune responses, and impaired intestinal mucosal barrier. Cumulative data show that nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) are dominant mediators in maintaining the homeostasis of the intestinal mucosal barrier, which play critical roles in sensing the commensal microbiota, maintaining homeostasis, and regulating intestinal inflammation. Blocking NLRs inflammasome activation by botanicals may be a promising way to prevent IBD progression. In this review, we systematically introduce the multiple roles of NLRs in regulating intestinal mucosal barrier homeostasis and focus on summarizing the activities and potential mechanisms of natural products against IBD. Aiming to propose new directions on the pathogenesis and precise treatment of IBD [ABSTRACT FROM AUTHOR]

Pattern recognition receptors are primitive sensors that arouse a preconfigured immune response to broad stimuli, including nonself pathogen-associated and autologous damage-associated molecular pattern molecules. These receptors are mainly expressed by innate myeloid cells, including granulocytes, monocytes, macrophages, and dendritic cells. Recent investigations have revealed new insights into these receptors as key players not only in triggering inflammation processes against pathogen invasion but also in mediating immune suppression in specific pathological states, including cancer. Myeloid-derived suppressor cells are preferentially expanded in many pathological conditions. This heterogeneous cell population includes immunosuppressive myeloid cells that are thought to be associated with poor prognosis and impaired response to immune therapies in various cancers. Identification of pattern recognition receptors and their ligands increases the understanding of immune-activating and immune-suppressive myeloid cell functions and sheds light on myeloid-derived suppressor cell differences from cognate granulocytes and monocytes in healthy conditions. This review summarizes the different expression, ligand recognition, signaling pathways, and cancer relations and identifies Toll-like receptors as potential new targets on myeloid-derived suppressor cells in cancer, which might help us to decipher the instruction codes for reverting suppressive myeloid cells toward an antitumor phenotype.

Filoviruses are a group of single-stranded negative sense RNA viruses. The most well-known filoviruses that affect humans are ebolaviruses and marburgviruses. During infection, they can cause life-threatening symptoms such as inflammation, tissue damage, and hemorrhagic fever, with case fatality rates as high as 90%. The innate immune system is the first line of defense against pathogenic insults such as filoviruses. Pattern recognition receptors (PRRs), including toll-like receptors, retinoic acid-inducible gene-I-like receptors, C-type lectin receptors, AIM2-like receptors, and NOD-like receptors, detect pathogens and activate downstream signaling to induce the production of proinflammatory cytokines and interferons, alert the surrounding cells to the threat, and clear infected and damaged cells through innate immune cell death. However, filoviruses can modulate the host inflammatory response and innate immune cell death, causing an aberrant immune reaction. Here, we discuss how the innate immune system senses invading filoviruses and how these deadly pathogens interfere with the immune response. Furthermore, we highlight the experimental difficulties of studying filoviruses as well as the current state of filovirus-targeting therapeutics. [ABSTRACT FROM AUTHOR]

The hepatocytes, as the main cells in the liver, exert liver functions by expressing innate immune receptors. The innate immune receptors include Toll-like receptors (TLRs), RIG-like receptors (retinoic acid inducible gene I-like receptors, RLRs) and NOD-like receptors (nucleotide binding oligomerization domain-like receptors, NLRs). The hepatocytes, recognize extracellular pathogen-associated molecular patterns (PAMPs) and intracellular damage-associated molecular patterns (DAMPs) through the above receptors. After the activation of the innate immune receptors, the hepatocytes produce cytokines, such as interferon (IFN), to protect the liver, through a series of signaling cascades. • The hepatocytes exert liver functions by expressing innate immune receptors. • The innate immune receptors include Toll-like receptors (TLRs), RIG-like receptors (RLRs) and NOD-like receptors (NLRs). • The hepatocytes recognize extracellular (PAMPs) and intracellular (DAMPs) through the innate immune receptors. • The hepatocytes produce cytokines to protect the liver, through a series of signaling cascades, after the activation of the innate immune receptors. [ABSTRACT FROM AUTHOR]

Abstract Background Plants in nature or crops in the field interact with a multitude of beneficial or parasitic organisms, including bacteria, fungi and viruses. Viruses are highly specialized to infect a limited range of host plants, leading in extreme cases to the full invasion of the host and a diseased phenotype. Resistance to viruses can be mediated by various passive or active mechanisms, including the RNA-silencing machinery and the innate immune system. Main text RNA-silencing mechanisms may inhibit viral replication, while viral components can elicit the innate immune system. Viruses that successfully enter the plant cell can elicit pattern-triggered immunity (PTI), albeit by yet unknown mechanisms. As a counter defense, viruses suppress PTI. Furthermore, viral Avirulence proteins (Avr) may be detected by intracellular immune receptors (Resistance proteins) to elicit effector-triggered immunity (ETI). ETI often culminates in a localized programmed cell death reaction, the hypersensitive response (HR), and is accompanied by a potent systemic defense response. In a dichotomous view, RNA silencing and innate immunity are seen as two separate mechanisms of resistance. Here, we review the intricate connections and similarities between these two regulatory systems, which are collectively required to ensure plant fitness and resilience. Conclusions The detailed understanding of immune regulation at the transcriptional level provides novel opportunities for enhancing plant resistance to viruses by RNA-based technologies. However, extensive use of RNA technologies requires a thorough understanding of the molecular mechanisms of RNA gene regulation. We describe the main examples of host RNA-mediated regulation of virus resistance.

Bread wheat is an essential crop with the second-highest global production after maize. Currently, wheat diseases are a serious threat to wheat production. Therefore, efficient breeding for disease resistance is extremely urgent in modern wheat. Here, we identified 2012 NLR genes from hexaploid wheat, and Ks values of paired syntenic NLRs showed a significant peak at 3.1–6.3 MYA, which exactly coincided with the first hybridization event between A and B genome lineages at ~5.5 MYA. We provided a landscape of dynamic diversity of NLRs from Triticum and Aegilops and found that NLR genes have higher diversity in wild progenitors and relatives. Further, most NLRs had opposite diversity patterns between genic and 2 Kb-promoter regions, which might respectively link sub/neofunctionalization and loss of duplicated NLR genes. Additionally, we identified an alien introgression of chromosome 4A in tetraploid emmer wheat, which was similar to that in hexaploid wheat. Transcriptome data from four experiments of wheat disease resistance helped to profile the expression pattern of NLR genes and identified promising NLRs involved in broad-spectrum disease resistance. Our study provided insights into the diversity evolution of NLR genes and identified beneficial NLRs to deploy into modern wheat in future wheat disease-resistance breeding.

Members of the mammalian Nod-like receptor (NLR) protein family are important intracellular sensors for bacteria. Bacteria have evolved under the pressure of detection by host immune sensing systems, leading to adaptive subversion strategies to dampen immune responses for their benefits. These include modification of microbe-associated molecular patterns (MAMPs), interception of innate immune pathways by secreted effector proteins and sophisticated instruction of anti-inflammatory adaptive immune responses. Here, we summarise our current understanding of subversion strategies used by bacterial pathogens to manipulate NLR-mediated responses, focusing on the well-studied members NOD1/2, and the inflammasome forming NLRs NLRC4, and NLRP3. We discuss how bacterial pathogens and their products activate these NLRs to promote inflammation and disease and the range of mechanisms used by bacterial pathogens to evade detection by NLRs and to block or dampen NLR activation to ultimately interfere with the generation of host immunity. Moreover, we discuss how bacteria utilise NLRs to facilitate immunotolerance and persistence in the host and outline how various mechanisms used to attenuate innate immune responses towards bacterial pathogens can also aid the host by reducing immunopathologies. Finally, we describe the therapeutic potential of harnessing immune subversion strategies used by bacteria to treat chronic inflammatory conditions. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis is a parasitic protozoan that causes trichomoniasis. The involvement of NLRP3 inflammasome in trichomoniasis has been discussed in recent studies. The present study aimed to find out the involvement of Nlrp3, Nlrc4, and Aim2 in the BALB/c mouse model infected with symptomatic and asymptomatic isolates of T. vaginalis by quantitative real-time PCR and immunohistochemistry. Our results showed a significantly increased expression of Nlrp3 in the vaginal tissue of the symptomatic group on the 2nd dpi and 14th dpi in the asymptomatic group, respectively. The cervical tissue of asymptomatic groups expressed higher Nlrp3 on 14th dpi than the symptomatic group. The Nlrc4 was expressed on 14th dpi in the vaginal and cervical tissues of mice infected with asymptomatic group as compared to the symptomatic group. Aim2 expression in vaginal tissue was highest at early time points in both the infected groups as compared to controls. However, in cervical tissues, a significant increase of Aim2 expression was observed on 14th dpi in asymptomatic as compared to the symptomatic group. The significantly higher expression of caspase-1 and caspase-4 was observed in cervical tissues of the asymptomatic group on 14th dpi as compared to the symptomatic group, respectively. All NLRs together resulted in higher IL-1β expression in the vaginal tissues of the symptomatic and asymptomatic groups. We conclude from this study that early expression of Nlrp3, Nlrc4, and Aim2 was seen in the symptomatic group as compared to the late-onset asymptomatic in the vaginal and cervical tissues. [ABSTRACT FROM AUTHOR]

Members of the mammalian Nod-like receptor (NLR) protein family are important intracellular sensors for bacteria. Bacteria have evolved under the pressure of detection by host immune sensing systems, leading to adaptive subversion strategies to dampen immune responses for their benefits. These include modification of microbe-associated molecular patterns (MAMPs), interception of innate immune pathways by secreted effector proteins and sophisticated instruction of anti-inflammatory adaptive immune responses. Here, we summarise our current understanding of subversion strategies used by bacterial pathogens to manipulate NLR-mediated responses, focusing on the well-studied members NOD1/2, and the inflammasome forming NLRs NLRC4, and NLRP3. We discuss how bacterial pathogens and their products activate these NLRs to promote inflammation and disease and the range of mechanisms used by bacterial pathogens to evade detection by NLRs and to block or dampen NLR activation to ultimately interfere with the generation of host immunity. Moreover, we discuss how bacteria utilise NLRs to facilitate immunotolerance and persistence in the host and outline how various mechanisms used to attenuate innate immune responses towards bacterial pathogens can also aid the host by reducing immunopathologies. Finally, we describe the therapeutic potential of harnessing immune subversion strategies used by bacteria to treat chronic inflammatory conditions.