RESUMEN
Ethylene response factors (ERFs) have been associated with biotic stress in Arabidopsis, while their function in non-model plants is still poorly understood. Here we investigated the role of potato ERF StPti5 in plant immunity. We show that StPti5 acts as a susceptibility factor. It negatively regulates potato immunity against potato virus Y and Ralstonia solanacearum, pathogens with completely different modes of action, and thereby has a different role than its orthologue in tomato. Remarkably, StPti5 is destabilised in healthy plants via the autophagy pathway and accumulates exclusively in the nucleus upon infection. We demonstrate that StEIN3 and StEIL1 directly bind the StPti5 promoter and activate its expression, while synergistic activity of the ethylene and salicylic acid pathways is required for regulated StPti expression. To gain further insight into the mode of StPti5 action in attenuating potato defence responses, we investigated transcriptional changes in salicylic acid deficient potato lines with silenced StPti5 expression. We show that StPti5 regulates the expression of other ERFs and downregulates the ubiquitin-proteasome pathway as well as several proteases involved in directed proteolysis. This study adds a novel element to the complex puzzle of immune regulation, by deciphering a two-level regulation of ERF transcription factor activity in response to pathogens.
Asunto(s)
Etilenos , Regulación de la Expresión Génica de las Plantas , Enfermedades de las Plantas , Inmunidad de la Planta , Proteínas de Plantas , Potyvirus , Regiones Promotoras Genéticas , Ralstonia solanacearum , Ácido Salicílico , Solanum tuberosum , Solanum tuberosum/microbiología , Solanum tuberosum/inmunología , Solanum tuberosum/genética , Solanum tuberosum/virología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Etilenos/metabolismo , Ralstonia solanacearum/fisiología , Enfermedades de las Plantas/microbiología , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/virología , Ácido Salicílico/metabolismo , Potyvirus/fisiología , Regiones Promotoras Genéticas/genética , Unión Proteica , Complejo de la Endopetidasa Proteasomal/metabolismo , Autofagia , Núcleo Celular/metabolismoRESUMEN
Toll-like receptors (TLRs) have become a focus in biomedicine and biomedical research given the roles of this unique family of innate immune proteins in immune activation, infection, and autoimmunity. It is evident that TLR dysregulation, and subsequent alterations in TLR-mediated inflammatory signalling, can contribute to disease pathogenesis, and TLR targeted therapies are in development. This review highlights evidence that cannabinoids are key regulators of TLR signalling. Cannabinoids include component of the plant Cannabis sativa L. (C. sativa), synthetic and endogenous ligands, and overall represent a class of compounds whose therapeutic potential and mechanism of action continues to be elucidated. Cannabinoid-based medicines are in the clinic, and are furthermore under intense investigation for broad clinical development to manage symptoms of a range of disorders. In this review, we present an overview of research evidence that signalling linked to a range of TLRs is targeted by cannabinoids, and such cannabinoid mediated effects represent therapeutic avenues for further investigation. First, we provide an overview of TLRs, adaptors and key signalling events, alongside a summary of evidence that TLRs are linked to disease pathologies. Next, we discuss the cannabinoids system and the development of cannabinoid-based therapeutics. Finally, for the bulk of this review, we systematically outline the evidence that cannabinoids (plant-derived cannabinoids, synthetic cannabinoids, and endogenous cannabinoid ligands) can cross-talk with innate immune signalling governed by TLRs, focusing specifically on each member of the TLR family. Cannabinoids should be considered as key regulators of signalling controlled by TLRs, and such regulation should be a major focus in terms of the anti-inflammatory propensity of the cannabinoid system.
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Cannabinoides , Cannabinoides/farmacología , Cannabinoides/uso terapéutico , Cannabinoides/metabolismo , Receptores Toll-Like , Transducción de Señal , Endocannabinoides , Moduladores de Receptores de Cannabinoides , Ligandos , Receptores de CannabinoidesRESUMEN
Sessile growing plants are always vulnerable to microbial pathogen attacks throughout their lives. To fend off pathogen invasion, plants have evolved a sophisticated innate immune system that consists of cell surface receptors and intracellular receptors. Somatic embryogenesis receptor kinases (SERKs) belong to a small group of leucine-rich repeat receptor-like kinases (LRR-RLKs) that function as co-receptors regulating diverse physiological processes. GENRAL REGULATORY FACTOR (GRF) proteins play an important role in physiological signalling transduction. However, the function of GRF proteins in plant innate immune signalling remains elusive. Here, we identified a GRF gene, GauGRF7, that is expressed both constitutively and in response to fungal pathogen infection. Intriguingly, silencing of GRF7 compromised plant innate immunity, resulting in susceptibility to Verticillium dahliae infection. Both transgenic GauGRF7 cotton and transgenic GauGRF7 Arabidopsis lines enhanced the innate immune response to V. dahliae infection, leading to high expression of two helper NLRs (hNLR) genes (ADR1 and NRG1) and pathogenesis-related genes, and increased ROS production and salicylic acid level. Moreover, GauGRF7 interacted with GhSERK1, which positively regulated GRF7-mediated innate immune response in cotton and Arabidopsis. Our findings revealed the molecular mechanism of the GRF protein in plant immune signaling and offer potential opportunities for improving plant resistance to V. dahliae infection.
Asunto(s)
Arabidopsis , Verticillium , Resistencia a la Enfermedad/genética , Verticillium/fisiología , Arabidopsis/metabolismo , Proteínas de Plantas/metabolismo , Transducción de Señal , Gossypium/genética , Gossypium/metabolismo , Enfermedades de las Plantas/microbiología , Regulación de la Expresión Génica de las PlantasRESUMEN
In the Drosophila testis, a group of stromal cells termed hub provides multiple niche signals for the surrounding germline and somatic stem cells. Stem cells of both populations compete for physical retention in the niche, and clones unable to transduce any one niche signal are rapidly eliminated from the stem cell pool by differentiation. We have mapped the transcriptomes of isolated somatic cyst stem cells and differentiated cyst cells, and found that the stem cells but not their differentiated progeny exhibit the signature of an innate immune response including the NF-κB transcription factor Relish (Rel). Related signalling pathways had previously implicated in cell competition in larval epithelia, prompting the question of whether NF-κB signalling was, despite the clear differences between the two competition scenarios, also involved in stem cell competition in the testis. Here we show i) that in the testis Rel is dispensable for stemness, ii) that loss of Rel or the upstream receptor Toll suppresses loser elimination following a variety of different triggers used to induce loser fate, and iii) that clonal Rel activation is sufficient for the displacement of neutral or winner cells from the niche, even if these cells otherwise retain stem cell properties.
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Quistes , Proteínas de Drosophila , Animales , Masculino , Drosophila/metabolismo , Testículo/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , FN-kappa B/metabolismo , Competencia Celular , Células Madre/metabolismo , Quistes/metabolismo , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismoRESUMEN
CCL2 is an inflammatory cytokine that regulates macrophage activity and is implicated in increased mammographic density and early breast tumorigenesis. The role of CCL2 in mediating stromal interactions that contribute to breast tumorigenesis has yet to be fully elucidated. THP-1-derived macrophages and mammary fibroblasts were co-cultured for 72 h. Fibroblasts and macrophages were analysed for phenotype, expression of inflammatory and ECM-regulatory genes and collagen production. Mice overexpressing CCL2 in the mammary glands were analysed for global gene expression by RNAseq at 12 weeks of age. These mice were cross-bred with PyMT mammary tumour mice to examine the role of CCL2 in tumorigenesis. The co-culture of macrophages with fibroblasts resulted in macrophage polarization towards an M2 phenotype, and upregulated expression of CCL2 and other genes associated with inflammation and ECM remodelling. CCL2 increased the production of insoluble collagen by fibroblasts. A global gene expression analysis of CCL2 overexpressing mice revealed that CCL2 upregulates cancer-associated gene pathways and downregulates fatty acid metabolism gene pathways. In the PyMT mammary tumour model, CCL2 overexpressing mice exhibited increased macrophage infiltration and early tumorigenesis. Interactions between macrophages and fibroblasts regulated by CCL2 can promote an environment that may increase breast cancer risk, leading to enhanced early tumorigenesis.
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Quimiocina CCL2 , Neoplasias , Ratones , Animales , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Macrófagos/metabolismo , Colágeno/metabolismo , Neoplasias/metabolismo , Carcinogénesis/metabolismoRESUMEN
BACKGROUND: Improved molecular diagnosis is needed in prostate cancer (PC). Fine needle aspiration (FNA) is a minimally invasive biopsy technique, less traumatic compared to core needle biopsy, and could be useful for diagnosis of PC. Molecular biomarkers (BMs) in FNA-samples can be assessed for prediction, eg of immunotherapy efficacy before treatment as well as at treatment decision time points during disease progression. METHODS: In the present pilot study, the expression levels of 151 BM proteins were analysed by proximity extension assay in FNA-samples from 16 patients, including benign prostate lesions (n = 3) and cancers (n = 13). An ensemble data analysis strategy was applied using several machine learning models. RESULTS: Twelve potentially predictive BM proteins correlating with International Society of Urological Pathology grade groups were identified, among them vimentin, tissue factor pathway inhibitor 2, and integrin beta-5. The validity of the results was supported by network analysis that showed functional associations between most of the identified putative BMs. We also showed that multiple immune checkpoint targets can be assessed (eg PD-L1, CD137, and Galectin-9), which may support the selection of immunotherapy in advanced PC. Results are promising but need further validation in a larger cohort. CONCLUSIONS: Our pilot study represents a "proof of concept" and shows that multiplex profiling of potential diagnostic and predictive BM proteins is feasible on tumour material obtained by FNA sampling of prostate cancer. Moreover, our results demonstrate that an ensemble data analysis strategy may facilitate the identification of BM signatures in pilot studies when the patient cohort is limited.
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Neoplasias de la Próstata , Masculino , Humanos , Biopsia con Aguja Fina , Proyectos Piloto , Neoplasias de la Próstata/patología , Próstata/patología , Biopsia con Aguja Gruesa , Biomarcadores/metabolismoRESUMEN
BACKGROUND: Heart failure (HF) is a complex pathophysiological state characterized by inadequate delivery of blood and nutrients to the cardiac tissues. It is rarely curable and is commonly associated with a poor prognosis. In this study, we aimed to analyse exomic and RNA-Seq data from patients with HF to identify the key altered pathways in HF. METHODS: Whole blood samples were collected from patients with HF and subjected to whole exome sequencing (WES) and RNA-Seq analysis. The gene expression and RNA-Seq data obtained were verified using gene chip analysis and RT-PCR. RESULTS: Both exomic and RNA-Seq data confirmed the dysregulation of phosphorylation and immune signalling in patients with HF. Specifically, exomic analysis showed that TITIN, OBSCURIN, NOD2, CDH2, MAP3K5, and SLC17A4 mutations were associated with HF, and RNA-Seq revealed that S100A12, S100A8, S100A9, PFDN5, and TMCC2, were upregulated in patients with HF. Additionally, comparison between RNA-seq and WES data showed that OAS1 mutations are associated with HF. CONLCUSION: Our findings indicated that patients with HF show an overall disruption of key phosphorylation and immune signalling pathways. Based on RNA-seq and WES, OAS1 mutations may be primarily responsible for these changes.
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Insuficiencia Cardíaca , Humanos , RNA-Seq , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/genética , Secuenciación del Exoma , Volumen Sistólico , Genómica , Mutación/genética , Perfilación de la Expresión Génica , 2',5'-Oligoadenilato SintetasaRESUMEN
PROBLEM: Recurrent pregnancy loss (RPL) is usually evaluated from a women's perspective, however, recent evidence implies involvement of male factors as paternally expressed genes predominate placenta. During fertilization, prior to implantation the immune system purposefully produces early pregnancy factors with potent immunomodulatory properties for adaptation to antigenically dissimilar embryo. Therefore, it is hypothesized that paternal immunological factors play a role in RPL. METHOD OF STUDY: Comparative proteome profiling (label free liquid chromatography mass spectroscopy: LC-MS/MS) of the seminal extracellular vesicles (SEVs), extracellular vesicle free seminal plasma (EVF-SP) and spermatozoa was carried out in semen of RPL patients (n = 21) and fertile donors (n = 21). This was followed by pathway and protein-protein interaction analysis, and validation of key proteins' expression (western blot). RESULTS: A total of 68, 28 and 49 differentially expressed proteins in SEVs, EVF-SP and spermatozoa of RPL patients, respectively, were found to be involved in inflammatory response, immune cell signalling and apoptosis. In SEVs, underexpressed GDF-15 and overexpressed C3 imply distorted maternal immune response to paternal antigens leading to impaired decidualization. Dysregulated TGFß signalling in EVF-SP surmises defective modulation of inflammatory response and induction of immune tolerance to seminal antigens in the female reproductive tract through generation of regulatory T cells. Retained histone variants in spermatozoa construe defective expression of early paternal genes, while underexpressed PTN may inflict defective angiogenesis resulting in expulsion of decidua. CONCLUSIONS: Impaired modulation of immune response and improper placental development due to altered cytokine levels in seminal components may be the contributing paternal factors in RPL.
Asunto(s)
Aborto Habitual , Proteoma , Humanos , Masculino , Femenino , Embarazo , Proteoma/metabolismo , Cromatografía Liquida , Placenta/metabolismo , Espectrometría de Masas en Tándem , Semen , Aborto Habitual/genética , Aborto Habitual/metabolismoRESUMEN
There is growing appreciation of key roles of the gut microbiota in maintaining homeostasis and influencing brain and behaviour at critical windows across the lifespan. Mounting evidence suggests that communication between the gut and the brain could be the key to understanding multiple neuropsychiatric disorders, with the immune system coming to the forefront as an important mechanistic mediator. Throughout the lifespan, the immune system exchanges continuous reciprocal signals with the central nervous system. Intestinal microbial cues alter immune mediators with consequences for host neurophysiology and behaviour. Several factors challenge the gut microbiota composition, which in response release molecules with neuro- and immuno-active potential that are crucial for adequate neuro-immune interactions. In this review, multiple factors contributing to the upkeep of the fine balance between health and disease of these systems are discussed, and we elucidate the potential mechanistic implications for the gut microbiota inputs on host brain and behaviour across the lifespan.
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Microbioma Gastrointestinal , Microbiota , Longevidad , Encéfalo/fisiología , Microbioma Gastrointestinal/fisiología , NeuroinmunomodulaciónRESUMEN
For many inflammatory cytokines, the response elicited is dependent on the recruitment of the tumour necrosis factor receptor-associated factor (TRAF) family of adaptor proteins. All TRAF proteins have a trimeric C-terminal TRAF domain, while at the N-terminus most TRAFs have a RING domain that forms dimers. The symmetry mismatch of the N- and C-terminal halves of TRAF proteins means that when receptors cluster, it is presumed that RING dimers connect TRAF trimers to form a network. Here, using purified TRAF6 proteins, we provide direct evidence in support of this model, and we show that TRAF6 trimers bind Lys63-linked ubiquitin chains to promote their processive assembly. This study provides critical evidence in support of TRAF trimers as key players in signalling.
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Transducción de Señal , Factor 6 Asociado a Receptor de TNF , Dimerización , Factor 6 Asociado a Receptor de TNF/genética , Factor 6 Asociado a Receptor de TNF/metabolismo , Ubiquitina/metabolismo , Dominios Proteicos , Factor 2 Asociado a Receptor de TNF/metabolismoRESUMEN
The expanding roles of macrophages in physiological and pathophysiological mechanisms now include normal tissue homeostasis, tissue repair and regeneration, including neuronal tissue; initiation, progression, and resolution of the inflammatory response and a diverse array of anti-microbial activities. Two hallmarks of macrophage activity which appear to be fundamental to their diverse cellular functionalities are cellular plasticity and phenotypic heterogeneity. Macrophage plasticity allows these cells to take on a broad spectrum of differing cellular phenotypes in response to local and possibly previous encountered environmental signals. Cellular plasticity also contributes to tissue- and stimulus-dependent macrophage heterogeneity, which manifests itself as different macrophage phenotypes being found at different tissue locations and/or after different cell stimuli. Together, plasticity and heterogeneity align macrophage phenotypes to their required local cellular functions and prevent inappropriate activation of the cell, which could lead to pathology. To execute the appropriate function, which must be regulated at the qualitative, quantitative, spatial and temporal levels, macrophages constantly monitor intracellular and extracellular parameters to initiate and control the appropriate cell signaling cascades. The sensors and signaling mechanisms which control macrophages are the focus of a considerable amount of research. Ion channels regulate the flow of ions between cellular membranes and are critical to cell signaling mechanisms in a variety of cellular functions. It is therefore surprising that the role of ion channels in the macrophage biology has been relatively overlooked. In this review we provide a summary of ion channel research in macrophages. We begin by giving a narrative-based explanation of the membrane potential and its importance in cell biology. We then report on research implicating different ion channel families in macrophage functions. Finally, we highlight some areas of ion channel research in macrophages which need to be addressed, future possible developments in this field and therapeutic potential.
RESUMEN
Potato virus Y (PVY) is an important pathogen of potato (Solanum tuberosum). Although the PBS1-RPS5 immune system is well documented in Arabidopsis thaliana, it has not been reported in potato. In Arabidopsis, the bacterial effector AvrPphB cleaves AtPBS1 to trigger an immune response. Here, we show that the AvrPphB-triggered immune response is mediated by StPBS1, a close homologue of AtPBS1 in potato. However, downstream signalling of StPBS1 was mediated by unknown resistance (R) proteins other than potato orthologues of AtRPS5 and HvPBR1, which is important for HvPBS1 signalling in barley. Immune signalling of StPBS1 is mediated by the AvrPphB C-terminal cleavage domain and an STKPQ motif, in contrast to AtPBS1-mediated immunity in which both AvrPphB cleavage fragments and an SEMPH motif are essential. The cleavage sequence of AvrPphB in StPBS1 was replaced with that of the PVY NIa-Pro protease to obtain StPBS1NIa . StPBS1NIa overexpression potato displayed stronger immunity to PVY infection than did the StPBS1 transgenic lines. StPBS1NIa was cleaved at the expected target site by NIa-Pro protease from PVY. Thus, we characterized the function of StPBS1 in potato immunity and provide a biotechnology control method for PVY via transformation of decoy-engineered StPBS1NIa .
Asunto(s)
Arabidopsis , Potyvirus , Solanum tuberosum , Virosis , Péptido Hidrolasas/metabolismo , Enfermedades de las Plantas , Potyvirus/metabolismoRESUMEN
The Toll/interleukin-1 receptor (TIR) domains are key innate immune signalling modules. Here, we present the crystal structure of the TIR domain of human interleukin-1 receptor 10 (IL-1R10), also called interleukin 1 receptor accessory protein like 2. It is similar to that of IL-1R9 (IL-1RAPL1) but shows significant structural differences to those from Toll-like receptors (TLRs) and the adaptor proteins MyD88 adaptor-like protein (MAL) and MyD88. Interactions of TIR domains in their respective crystals and the higher-order assemblies (MAL and MyD88) reveal the presence of a common 'BCD surface', suggesting its functional significance. We also show that the TIR domains of IL-1R10 and IL-1R9 lack NADase activity, consistent with their structures. Our study provides a foundation for unravelling the functions of IL-1R9 and IL-1R10.
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Proteína Accesoria del Receptor de Interleucina-1/química , Factor 88 de Diferenciación Mieloide , Receptores de Interleucina-1 , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Humanos , Glicoproteínas de Membrana/metabolismo , Estructura Terciaria de Proteína , Receptores de Interleucina-1/genética , Transducción de SeñalRESUMEN
Ester-linked ubiquitination of serine or threonine residues - or even lipids - has emerged as a new regulatory earmark in cell signalling. Petrova et al. (2021) now reveal that ubiquitin esterification by the atypical ubiquitin ligase HOIL-1, a component of the LUBAC complex, is critical for proper formation of linear ubiquitin chains and control of immune signalling in T cells and macrophages. Surprisingly, ester-linked ubiquitination can either promote or inhibit linear ubiquitin conjugation and cytokine production depending on the receptor and immune cell engaged. Comment on: https://doi.org/10.1111/febs.15896.
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Ésteres , Ubiquitina , Transducción de Señal , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , UbiquitinaciónRESUMEN
Bombyx mori is a model species of Lepidoptera, in which 21 gene families and 220 genes have been identified as involved in immunity. However, only 45 B. mori - Drosophila melanogaster - Anopheles gambiae - Apis mellifera - Tribolium castaneum 1:1:1:1:1 orthologous genes were identified. B. mori has unique immune factors not found in D. melanogaster - A. gambiae - A. mellifera - T. castaneum. Pattern recognition receptors, signal transducers and effector genes for antifungal immune responses in B. mori have evolved through expansion and modification of existing genes. This review summarizes the current knowledge of the antifungal immune responses of B. mori and focuses on the lineage-specific gene evolution used by Lepidoptera to adapt to the challenge by pathogens, especially entomopathogenic fungi.
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Bombyx/inmunología , Micosis/inmunología , Receptores de Reconocimiento de Patrones/metabolismo , Adaptación Fisiológica , Animales , Evolución Molecular , Interacciones Huésped-Patógeno , Humanos , Inmunidad Innata , Transducción de SeñalRESUMEN
Insects possess an immune system that protects them from attacks by various pathogenic microorganisms that would otherwise threaten their survival. Immune mechanisms may deal directly with the pathogens by eliminating them from the host organism or disarm them by suppressing the synthesis of toxins and virulence factors that promote the invasion and destructive action of the intruder within the host. Insects have been established as outstanding models for studying immune system regulation because innate immunity can be explored as an integrated system at the level of the whole organism. Innate immunity in insects consists of basal immunity that controls the constitutive synthesis of effector molecules such as antimicrobial peptides, and inducible immunity that is activated after detection of a microbe or its product(s). Activation and coordination of innate immune defenses in insects involve evolutionary conserved immune factors. Previous research in insects has led to the identification and characterization of distinct immune signalling pathways that modulate the response to microbial infections. This work has not only advanced the field of insect immunology, but it has also rekindled interest in the innate immune system of mammals. Here we review the current knowledge on key molecular components of insect immunity and discuss the opportunities they present for confronting infectious diseases in humans.
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Péptidos Antimicrobianos/inmunología , Inmunidad Innata , Proteínas de Insectos/inmunología , Insectos/inmunología , Transducción de Señal/inmunología , AnimalesRESUMEN
Antifungal innate immunity is an important defence used by insects against entomogenous fungi. However, the downstream target antifungal peptides of different immune signalling pathways are unknown. We found that the Toll, Janus kinase/signal transducer and activator of transcription (Jak/STAT) and Immunodeficiency (IMD) signalling pathways in the silkworm, Bombyx mori, can be activated by Beauveria bassiana. Inhibition of the Toll, IMD and Jak/STAT signalling pathways reduced the antifungal activities of silkworm haemolymph. We verified the target antifungal peptides of different immune signalling pathways. The expression patterns of five anti-fungal peptide genes in silkworm larvae and BmN cells were detected after blocking or over-expressing the immune signalling pathways. The Toll signalling pathways mediated the expression of Bmcecropin A, Bmattacin 1 and Bmgloverin 2; IMD signalling pathways mediated Bmenbocin 1, Bmgloverin 2 and Bmattacin 1; Jak/STAT signalling pathways mediated Bmstorage protein 30K-19G1 (Bmsp 1), Bmattacin 1 and Bmcecropin A. These data indicated that anti-microbial peptide genes in B. mori evolved through expansion and selection of existing genes to adapt to the challenge of invasive microorganisms such as fungi. This information provides insight into the antifungal immune responses in B. mori and aids understanding of insect immune regulation mechanisms.
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Beauveria/inmunología , Bombyx , Proteínas Citotóxicas Formadoras de Poros/metabolismo , Transducción de Señal/inmunología , Animales , Bombyx/genética , Bombyx/inmunología , Bombyx/metabolismo , Bombyx/microbiología , Genes de Insecto , Hemolinfa/metabolismo , Interacciones Microbiota-Huesped , Inmunidad Innata/genética , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Filogenia , Proteínas Citotóxicas Formadoras de Poros/genéticaRESUMEN
DNA damage is the cause of numerous human pathologies including cancer, premature aging, and chronic inflammatory conditions. The DNA damage response (DDR), in turn, coordinates DNA damage checkpoint activation and promotes the removal of DNA lesions. In recent years, several studies have shown how the DDR and the immune system are tightly connected, revealing an important crosstalk between the two of them. This interesting interplay has opened up new perspectives in clinical studies for immunological diseases as well as for cancer treatment. In this review, we provide an overview, from cellular to molecular pathways, on how DDR and the immune system communicate and share the crucial commitment of maintaining the genomic fitness.
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Daño del ADN , Interacciones Huésped-Patógeno/genética , Interacciones Huésped-Patógeno/inmunología , Inmunidad , Animales , Biomarcadores , Susceptibilidad a Enfermedades , Humanos , Inmunidad Innata , Inflamación/etiología , Inflamación/metabolismo , Terapia Molecular Dirigida , Neoplasias/tratamiento farmacológico , Neoplasias/etiología , Neoplasias/radioterapia , Estrés Oxidativo , Transducción de SeñalRESUMEN
The intracellular nucleotide-binding domain leucine-rich repeat (NLR) class of immune receptors plays an important role in plant viral defence. Plant NLRs recognize viruses through direct or indirect association of viral proteins, triggering a downstream defence response to prevent viral proliferation and movement within the plant. This review focuses on current knowledge of intracellular perception of viral pathogens, activation of NLRs and the downstream signalling components involved in plant viral defence.