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1.
Front Immunol ; 12: 636118, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854506

RESUMO

Following respiratory viral infections or local immunizations, lung resident-memory T cells (TRM) of the CD8 lineage provide protection against the same pathogen or related pathogens with cross-reactive T cell epitopes. Yet, it is now clear that, if homeostatic controls are lost following viral pneumonia, CD8 TRM cells can mediate pulmonary pathology. We recently showed that the aging process can result in loss of homeostatic controls on CD8 TRM cells in the respiratory tract. This may be germane to treatment modalities in both influenza and coronavirus disease 2019 (COVID-19) patients, particularly, the portion that present with symptoms linked to long-lasting lung dysfunction. Here, we review the developmental cues and functionalities of CD8 TRM cells in viral pneumonia models with a particular focus on their capacity to mediate heterogeneous responses of immunity and pathology depending on immune status.


Assuntos
Linfócitos T CD8-Positivos/imunologia , /virologia , Memória Imunológica , Pulmão/imunologia , Pulmão/virologia , /imunologia , Fatores Etários , Animais , Biomarcadores , Linfócitos T CD8-Positivos/metabolismo , /patologia , Resistência à Doença/imunologia , Homeostase , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunofenotipagem , Pulmão/metabolismo , Pulmão/patologia , Contagem de Linfócitos , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/patologia
2.
Int J Mol Sci ; 22(6)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803699

RESUMO

Leaf rust and powdery mildew are two important foliar diseases in wheat. A recombinant inbred line (RIL) population, obtained by crossing two bread wheat cultivars ('Victo' and 'Spada'), was evaluated for resistance to the two pathogens at seedling stage. Upon developing a genetic map of 8726 SNP loci, linkage analysis identified three resistance Quantitative Trait Loci (QTLs), with 'Victo' contributing the resistant alleles to all loci. One major QTL (QPm.gb-7A) was detected in response to Blumeria graminis on chromosome 7A, which explained 90% of phenotypic variation (PV). The co-positional relationship with known powdery mildew (Pm) resistance loci suggested that a new source of resistance was identified in T. aestivum. Two QTLs were detected in response to Puccinia triticina: a major gene on chromosome 5D (QLr.gb-5D), explaining a total PV of about 59%, and a minor QTL on chromosome 2B (QLr.gb-2B). A positional relationship was observed between the QLr.gb-5D with the known Lr1 gene, but polymorphisms were found between the cloned Lr1 and the corresponding 'Victo' allele, suggesting that QLr.gb-5D could represent a new functional Lr1 allele. Lastly, upon anchoring the QTL on the T. aestivum reference genome, candidate genes were hypothesized on the basis of gene annotation and in silico gene expression analysis.


Assuntos
Ascomicetos/fisiologia , Resistência à Doença/imunologia , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Folhas de Planta/microbiologia , Triticum/imunologia , Triticum/microbiologia , Sequência de Aminoácidos , Ascomicetos/isolamento & purificação , Pão , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Simulação por Computador , Cruzamentos Genéticos , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Marcadores Genéticos , Fenótipo , Proteínas de Plantas/química , Proteínas de Plantas/genética , Locos de Características Quantitativas/genética
3.
Int J Mol Sci ; 22(2)2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33467397

RESUMO

Mycobacterium abscessus (Mab) is an emerging, nontuberculosis mycobacterium (NTM) that infects humans. Mab has two morphotypes, smooth (S) and rough (R), related to the production of glycopeptidolipid (GPL), that differ in pathogenesis. To further understand the pathogenicity of these morphotypes in vivo, the amphibian Xenopus laevis was used as an alternative animal model. Mab infections have been previously modeled in zebrafish embryos and mice, but Mab are cleared early from immunocompetent mice, preventing the study of chronic infection, and the zebrafish model cannot be used to model a pulmonary infection and T cell involvement. Here, we show that X. laevis tadpoles, which have lungs and T cells, can be used as a complementary model for persistent Mab infection and pathogenesis. Intraperitoneal (IP) inoculation of S and R Mab morphotypes disseminated to tadpole tissues including liver and lungs, persisting for up to 40 days without significant mortality. Furthermore, the R morphotype was more persistent, maintaining a higher bacterial load at 40 days postinoculation. In contrast, the intracardiac (IC) inoculation with S Mab induced significantly greater mortality than inoculation with the R Mab form. These data suggest that X. laevis tadpoles can serve as a useful comparative experimental organism to investigate pathogenesis and host resistance to M. abscessus.


Assuntos
Modelos Animais de Doenças , Mycobacterium abscessus/metabolismo , Xenopus laevis/crescimento & desenvolvimento , Animais , Resistência à Doença/imunologia , Interações Hospedeiro-Patógeno , Humanos , Larva/crescimento & desenvolvimento , Larva/imunologia , Larva/microbiologia , Fígado/imunologia , Fígado/microbiologia , Pulmão/imunologia , Pulmão/microbiologia , Camundongos Endogâmicos C57BL , Infecções por Mycobacterium não Tuberculosas/genética , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/classificação , Mycobacterium abscessus/patogenicidade , Linfócitos T/imunologia , Linfócitos T/microbiologia , Fatores de Tempo , Virulência , Xenopus laevis/imunologia , Xenopus laevis/microbiologia
4.
Int J Biol Macromol ; 172: 309-320, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33454323

RESUMO

Ribonuclease 1 (RNase1) is a vertebrate-specific enzyme that mainly performs digestive activity in herbivorous mammals. Here we used bacterial viability assays to explore its antimicrobial activity in blunt snout bream (Megalobrama amblycephala). The results showed that Ma-RNase1 rapidly killed Gram-negative and Gram-positive bacteria at micromolar concentrations. Ma-RNase1 increased the permeability of bacterial outer and inner membranes, thus reducing the integrity of bacterial cell wall and membrane. Moreover, Ma-RNase1 effectively counteracted the tissue damage and apoptosis caused by Aeromonas hydrophila infection. Quantitative real-time PCR and immunoblot analysis indicated that RNase1 mRNA and protein were up-regulated in the kidney and gut during infection. Furthermore, A. hydrophila infection significantly induced Tnf-α and Il-1ß mRNA expression in liver, but not in the RNase1 pre-treatment group. In addition, a significant increase in the expression of immune-related genes (Nf-κb and Tlr4) was found in liver, kidney and gut of A. hydrophila-infected fish, while a decrease in Myd88 and Tlr4 levels was found in liver, spleen, kidney and gut in the group pre-treated with RNase1. Collectively, these data suggest that Ma-RNase1 has antimicrobial function both in vitro and in vivo, and contributes to the protective effect and immune defense of blunt snout bream.


Assuntos
Aeromonas hydrophila/imunologia , Cyprinidae/genética , Doenças dos Peixes/genética , Proteínas de Peixes/genética , Infecções por Bactérias Gram-Negativas/genética , Ribonucleases/genética , Aeromonas hydrophila/crescimento & desenvolvimento , Aeromonas hydrophila/patogenicidade , Animais , Membrana Celular/imunologia , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular , Cyprinidae/imunologia , Cyprinidae/microbiologia , Resistência à Doença/genética , Resistência à Doença/imunologia , Doenças dos Peixes/enzimologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/patologia , Proteínas de Peixes/imunologia , Regulação da Expressão Gênica , Infecções por Bactérias Gram-Negativas/enzimologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/patologia , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Intestinos/imunologia , Intestinos/microbiologia , Rim/imunologia , Rim/microbiologia , Fígado/imunologia , Fígado/microbiologia , Viabilidade Microbiana , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/imunologia , NF-kappa B/genética , NF-kappa B/imunologia , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Ribonucleases/imunologia , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
5.
Nat Commun ; 12(1): 705, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514716

RESUMO

Plant genomes encode hundreds of receptor kinases and peptides, but the number of known plant receptor-ligand pairs is limited. We report that the Arabidopsis leucine-rich repeat receptor kinase LRR-RK MALE DISCOVERER 1-INTERACTING RECEPTOR LIKE KINASE 2 (MIK2) is the receptor for the SERINE RICH ENDOGENOUS PEPTIDE (SCOOP) phytocytokines. MIK2 is necessary and sufficient for immune responses triggered by multiple SCOOP peptides, suggesting that MIK2 is the receptor for this divergent family of peptides. Accordingly, the SCOOP12 peptide directly binds MIK2 and triggers complex formation between MIK2 and the BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1) co-receptor. MIK2 is required for resistance to the important root pathogen Fusarium oxysporum. Notably, we reveal that Fusarium proteomes encode SCOOP-like sequences, and corresponding synthetic peptides induce MIK2-dependent immune responses. These results suggest that MIK2 may recognise Fusarium-derived SCOOP-like sequences to induce immunity against Fusarium. The definition of SCOOPs as MIK2 ligands will help to unravel the multiple roles played by MIK2 during plant growth, development and stress responses.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/imunologia , Proteínas Fúngicas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Doenças das Plantas/imunologia , Proteínas Quinases/metabolismo , Receptores de Superfície Celular/metabolismo , Arabidopsis/metabolismo , Arabidopsis/microbiologia , Proteínas de Arabidopsis/imunologia , Clonagem Molecular , Resistência à Doença/imunologia , Proteínas Fúngicas/imunologia , Fusarium/imunologia , Fusarium/metabolismo , Fusarium/patogenicidade , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Ligantes , Doenças das Plantas/microbiologia , Raízes de Plantas/imunologia , Raízes de Plantas/metabolismo , Raízes de Plantas/microbiologia , Plantas Geneticamente Modificadas , Proteínas Quinases/imunologia , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Superfície Celular/imunologia , Transdução de Sinais/imunologia , Tabaco/genética , Tabaco/imunologia
6.
Elife ; 92020 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-33357377

RESUMO

Organisms rely on inducible and constitutive immune defences to combat infection. Constitutive immunity enables a rapid response to infection but may carry a cost for uninfected individuals, leading to the prediction that it will be favoured when infection rates are high. When we exposed populations of Drosophila melanogaster to intense parasitism by the parasitoid wasp Leptopilina boulardi, they evolved resistance by developing a more reactive cellular immune response. Using single-cell RNA sequencing, we found that immune-inducible genes had become constitutively upregulated. This was the result of resistant larvae differentiating precursors of specialized immune cells called lamellocytes that were previously only produced after infection. Therefore, populations evolved resistance by genetically hard-wiring the first steps of an induced immune response to become constitutive.


Assuntos
Evolução Biológica , Resistência à Doença/imunologia , Drosophila melanogaster/imunologia , Imunidade Celular/imunologia , Infecções/imunologia , Animais , Resistência à Doença/genética , Drosophila melanogaster/parasitologia , Feminino , Regulação da Expressão Gênica , Hemócitos/imunologia , Larva/imunologia , Masculino , Vespas
7.
Viruses ; 12(12)2020 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-33353088

RESUMO

Innate immune sensors and restriction factors are cellular proteins that synergize to build an effective first line of defense against viral infections. Innate sensors are usually constitutively expressed and capable of detecting pathogen-associated molecular patterns (PAMPs) via specific pattern recognition receptors (PRRs) to stimulate the immune response. Restriction factors are frequently upregulated by interferons (IFNs) and may inhibit viral pathogens at essentially any stage of their replication cycle. Members of the Pyrin and hematopoietic interferon-inducible nuclear (HIN) domain (PYHIN) family have initially been recognized as important sensors of foreign nucleic acids and activators of the inflammasome and the IFN response. Accumulating evidence shows, however, that at least three of the four members of the human PYHIN family restrict viral pathogens independently of viral sensing and innate immune activation. In this review, we provide an overview on the role of human PYHIN proteins in the innate antiviral immune defense and on viral countermeasures.


Assuntos
Resistência à Doença , Interações Hospedeiro-Patógeno , Proteínas Nucleares/metabolismo , Viroses/metabolismo , Animais , Resistência à Doença/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/genética , Família Multigênica , Proteínas Nucleares/genética , Viroses/imunologia , Viroses/virologia
8.
Int J Mol Sci ; 22(1)2020 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-33375472

RESUMO

Systemic Acquired Resistance (SAR) improves immunity of plant systemic tissue after local exposure to a pathogen. Guard cells that form stomatal pores on leaf surfaces recognize bacterial pathogens via pattern recognition receptors, such as Flagellin Sensitive 2 (FLS2). However, how SAR affects stomatal immunity is not known. In this study, we aim to reveal molecular mechanisms underlying the guard cell response to SAR using multi-omics of proteins, metabolites and lipids. Arabidopsis plants previously exposed to pathogenic bacteria Pseudomonas syringae pv. tomato DC3000 (Pst) exhibit an altered stomatal response compared to control plants when they are later exposed to the bacteria. Reduced stomatal apertures of SAR primed plants lead to decreased number of bacteria in leaves. Multi-omics has revealed molecular components of SAR response specific to guard cells functions, including potential roles of reactive oxygen species (ROS) and fatty acid signaling. Our results show an increase in palmitic acid and its derivative in the primed guard cells. Palmitic acid may play a role as an activator of FLS2, which initiates stomatal immune response. Improved understanding of how SAR signals affect stomatal immunity can aid biotechnology and marker-based breeding of crops for enhanced disease resistance.


Assuntos
Arabidopsis/imunologia , Resistência à Doença/imunologia , Lipidômica , Metabolômica , Doenças das Plantas/imunologia , Estômatos de Plantas/metabolismo , Proteoma/metabolismo , Pseudomonas syringae/crescimento & desenvolvimento , Arabidopsis/metabolismo , Arabidopsis/microbiologia , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Clorofila/metabolismo , Cromatografia Líquida , Ácidos Graxos/metabolismo , Espectrometria de Massas , Ácidos Palmíticos/metabolismo , Doenças das Plantas/microbiologia , Folhas de Planta/metabolismo , Folhas de Planta/microbiologia , Estômatos de Plantas/imunologia , Estômatos de Plantas/microbiologia , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Pseudomonas syringae/imunologia , Pseudomonas syringae/patogenicidade , Espécies Reativas de Oxigênio/metabolismo
9.
PLoS Biol ; 18(9): e3000783, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32925907

RESUMO

Plant nucleotide-binding (NB) leucine-rich repeat (LRR) receptor (NLR) proteins function as intracellular immune receptors that perceive the presence of pathogen-derived virulence proteins (effectors) to induce immune responses. The 2 major types of plant NLRs that "sense" pathogen effectors differ in their N-terminal domains: these are Toll/interleukin-1 receptor resistance (TIR) domain-containing NLRs (TNLs) and coiled-coil (CC) domain-containing NLRs (CNLs). In many angiosperms, the RESISTANCE TO POWDERY MILDEW 8 (RPW8)-CC domain containing NLR (RNL) subclass of CNLs is encoded by 2 gene families, ACTIVATED DISEASE RESISTANCE 1 (ADR1) and N REQUIREMENT GENE 1 (NRG1), that act as "helper" NLRs during multiple sensor NLR-mediated immune responses. Despite their important role in sensor NLR-mediated immunity, knowledge of the specific, redundant, and synergistic functions of helper RNLs is limited. We demonstrate that the ADR1 and NRG1 families act in an unequally redundant manner in basal resistance, effector-triggered immunity (ETI) and regulation of defense gene expression. We define RNL redundancy in ETI conferred by some TNLs and in basal resistance against virulent pathogens. We demonstrate that, in Arabidopsis thaliana, the 2 RNL families contribute specific functions in ETI initiated by specific CNLs and TNLs. Time-resolved whole genome expression profiling revealed that RNLs and "classical" CNLs trigger similar transcriptome changes, suggesting that RNLs act like other CNLs to mediate ETI downstream of sensor NLR activation. Together, our genetic data confirm that RNLs contribute to basal resistance, are fully required for TNL signaling, and can also support defense activation during CNL-mediated ETI.


Assuntos
Arabidopsis/imunologia , Proteínas NLR/fisiologia , Imunidade Vegetal/genética , Receptores Imunológicos/fisiologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/fisiologia , Resistência à Doença/genética , Resistência à Doença/imunologia , Regulação da Expressão Gênica de Plantas , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/fisiologia , Família Multigênica/genética , Família Multigênica/fisiologia , Proteínas NLR/genética , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Plantas Geneticamente Modificadas , Receptores Imunológicos/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Transcriptoma
10.
PLoS One ; 15(8): e0236633, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785249

RESUMO

The induction of general plant defense responses following the perception of external elicitors is now regarded as the first level of the plant immune response. Depending on the involvement or not of these molecules in pathogenicity, this induction of defense is called either Pathogen-Associated Molecular Pattern (PAMP) Triggered Immunity or Pattern Triggered Immunity-both abbreviated to PTI. Because PTI is assumed to be a widespread and stable form of resistance to infection, understanding the mechanisms driving it becomes a major goal for the sustainable management of plant-pathogen interactions. However, the induction of PTI is complex. Our hypotheses are that (i) the recognition by the plant of PAMPs vs non-PAMP elicitors leads to specific defense profiles and (ii) the responses specifically induced by PAMPs target critical life history traits of the pathogen that produced them. We thus analyzed, using a metabolomic approach coupled with transcriptomic and hormonal analyses, the defense profiles induced in potato foliage treated with either a Concentrated Culture Filtrate (CCF) from Phytophthora infestans or two non-PAMP preparations, ß-aminobutyric acid (BABA) and an Ulva spp. Extract, used separately. Each elicitor induced specific defense profiles. CCF up-regulated sesquiterpenes but down-regulated sterols and phenols, notably α-chaconine, caffeoyl quinic acid and rutin, which decreased spore production of P. infestans in vitro. CCF thus induces both defense and counter-defense responses. By contrast, the Ulva extract triggered the synthesis of a large-spectrum of antimicrobial compounds through the phenylpropanoid/flavonoid pathways, while BABA targeted the primary metabolism. Hence, PTI can be regarded as a heterogeneous set of general and pathogen-specific responses triggered by the molecular signatures of each elicitor, rather than as a uniform, non-specific and broad-spectrum set of general defense reactions.


Assuntos
Resistência à Doença/imunologia , Doenças das Plantas/imunologia , Imunidade Vegetal/imunologia , Solanum tuberosum/imunologia , Aminobutiratos/farmacologia , Resistência à Doença/efeitos dos fármacos , Flavonoides/biossíntese , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Fenóis/metabolismo , Phytophthora infestans/imunologia , Phytophthora infestans/patogenicidade , Doenças das Plantas/microbiologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Imunidade Vegetal/efeitos dos fármacos , Sesquiterpenos/metabolismo , Solanum tuberosum/crescimento & desenvolvimento , Solanum tuberosum/microbiologia , Esteróis/metabolismo , Ulva/química
11.
Immunol Lett ; 226: 38-45, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32659267

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative pathogen of deadly Coronavirus disease-19 (COVID-19) pandemic, which emerged as a major threat to public health across the world. Although there is no clear gender or socioeconomic discrimination in the incidence of COVID-19, individuals who are older adults and/or with comorbidities and compromised immunity have a relatively higher risk of contracting this disease. Since no specific drug has yet been discovered, strengthening immunity along with maintaining a healthy living is the best way to survive this disease. As a healthy practice, calorie restriction in the form of intermittent fasting (IF) in several clinical settings has been reported to promote several health benefits, including priming of the immune response. This dietary restriction also activates autophagy, a cell surveillance system that boosts up immunity. With these prevailing significance in priming host defense, IF could be a potential strategy amid this outbreak to fighting off SARS-CoV-2 infection. Currently, no review so far available proposing IF as an encouraging strategy in the prevention of COVID-19. A comprehensive review has therefore been planned to highlight the beneficial role of fasting in immunity and autophagy, that underlie the possible defense against SARS-CoV-2 infection. The COVID-19 pathogenesis and its impact on host immune response have also been briefly outlined. This review aimed at revisiting the immunomodulatory potential of IF that may constitute a promising preventive approach against COVID-19.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/etiologia , Infecções por Coronavirus/metabolismo , Suscetibilidade a Doenças , Jejum , Interações Hospedeiro-Patógeno , Pneumonia Viral/etiologia , Pneumonia Viral/metabolismo , Autofagia , Restrição Calórica , Resistência à Doença/imunologia , Suscetibilidade a Doenças/imunologia , Jejum/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Evasão da Resposta Imune , Imunidade , Pandemias
12.
Nat Commun ; 11(1): 3763, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32724132

RESUMO

In both animals and plants, the perception of bacterial flagella by immune receptors elicits the activation of defence responses. Most plants are able to perceive the highly conserved epitope flg22 from flagellin, the main flagellar protein, from most bacterial species. However, flagellin from Ralstonia solanacearum, the causal agent of the bacterial wilt disease, presents a polymorphic flg22 sequence (flg22Rso) that avoids perception by all plants studied to date. In this work, we show that soybean has developed polymorphic versions of the flg22 receptors that are able to perceive flg22Rso. Furthermore, we identify key residues responsible for both the evasion of perception by flg22Rso in Arabidopsis and the gain of perception by the soybean receptors. Heterologous expression of the soybean flg22 receptors in susceptible plant species, such as tomato, enhances resistance to bacterial wilt disease, demonstrating the potential of these receptors to enhance disease resistance in crop plants.


Assuntos
Flagelina/imunologia , Imunidade Vegetal , Proteínas de Plantas/imunologia , Receptores Imunológicos/imunologia , Soja/imunologia , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Arabidopsis/genética , Arabidopsis/imunologia , Arabidopsis/metabolismo , Resistência à Doença/genética , Resistência à Doença/imunologia , Epitopos/imunologia , Flagelina/genética , Flagelina/metabolismo , Evasão da Resposta Imune/genética , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas , Polimorfismo Genético/imunologia , Ralstonia solanacearum/imunologia , Ralstonia solanacearum/patogenicidade , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Soja/genética , Soja/metabolismo , Soja/microbiologia
13.
Nat Immunol ; 21(8): 857-867, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32601469

RESUMO

Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by homozygous or compound heterozygous gain-of-function mutations in MEFV, which encodes pyrin, an inflammasome protein. Heterozygous carrier frequencies for multiple MEFV mutations are high in several Mediterranean populations, suggesting that they confer selective advantage. Among 2,313 Turkish people, we found extended haplotype homozygosity flanking FMF-associated mutations, indicating evolutionarily recent positive selection of FMF-associated mutations. Two pathogenic pyrin variants independently arose >1,800 years ago. Mutant pyrin interacts less avidly with Yersinia pestis virulence factor YopM than with wild-type human pyrin, thereby attenuating YopM-induced interleukin (IL)-1ß suppression. Relative to healthy controls, leukocytes from patients with FMF harboring homozygous or compound heterozygous mutations and from asymptomatic heterozygous carriers released heightened IL-1ß specifically in response to Y. pestis. Y. pestis-infected MefvM680I/M680I FMF knock-in mice exhibited IL-1-dependent increased survival relative to wild-type knock-in mice. Thus, FMF mutations that were positively selected in Mediterranean populations confer heightened resistance to Y. pestis.


Assuntos
Resistência à Doença/genética , Febre Familiar do Mediterrâneo/genética , Peste , Pirina/genética , Seleção Genética/genética , Animais , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas da Membrana Bacteriana Externa/metabolismo , Resistência à Doença/imunologia , Haplótipos , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Peste/imunologia , Peste/metabolismo , Pirina/imunologia , Pirina/metabolismo , Turquia , Fatores de Virulência/imunologia , Fatores de Virulência/metabolismo , Yersinia pestis
14.
Nat Commun ; 11(1): 3334, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620760

RESUMO

TH17 cells exemplify environmental immune adaptation: they can acquire both a pathogenic and an anti-inflammatory fate. However, it is not known whether the anti-inflammatory fate is merely a vestigial trait, or whether it serves to preserve the integrity of the host tissues. Here we show that the capacity of TH17 cells to acquire an anti-inflammatory fate is necessary to sustain immunological tolerance, yet it impairs immune protection against S. aureus. Additionally, we find that TGF-ß signalling via Smad3/Smad4 is sufficient for the expression of the anti-inflammatory cytokine, IL-10, in TH17 cells. Our data thus indicate a key function of TH17 cell plasticity in maintaining immune homeostasis, and dissect the molecular mechanisms explaining the functional flexibility of TH17 cells with regard to environmental changes.


Assuntos
Homeostase/imunologia , Inflamação/imunologia , Interleucina-10/imunologia , Intestinos/imunologia , Células Th17/imunologia , Animais , Plasticidade Celular/imunologia , Resistência à Doença/genética , Resistência à Doença/imunologia , Células HEK293 , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-17/genética , Interleucina-17/imunologia , Interleucina-17/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/imunologia , Staphylococcus aureus/fisiologia , Células Th17/metabolismo , Fator de Crescimento Transformador beta/imunologia , Fator de Crescimento Transformador beta/metabolismo
15.
Proc Natl Acad Sci U S A ; 117(30): 18099-18109, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32669441

RESUMO

Quantitative disease resistance (QDR) represents the predominant form of resistance in natural populations and crops. Surprisingly, very limited information exists on the biomolecular network of the signaling machineries underlying this form of plant immunity. This lack of information may result from its complex and quantitative nature. Here, we used an integrative approach including genomics, network reconstruction, and mutational analysis to identify and validate molecular networks that control QDR in Arabidopsis thaliana in response to the bacterial pathogen Xanthomonas campestris To tackle this challenge, we first performed a transcriptomic analysis focused on the early stages of infection and using transgenic lines deregulated for the expression of RKS1, a gene underlying a QTL conferring quantitative and broad-spectrum resistance to X campestris RKS1-dependent gene expression was shown to involve multiple cellular activities (signaling, transport, and metabolism processes), mainly distinct from effector-triggered immunity (ETI) and pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) responses already characterized in A thaliana Protein-protein interaction network reconstitution then revealed a highly interconnected and distributed RKS1-dependent network, organized in five gene modules. Finally, knockout mutants for 41 genes belonging to the different functional modules of the network revealed that 76% of the genes and all gene modules participate partially in RKS1-mediated resistance. However, these functional modules exhibit differential robustness to genetic mutations, indicating that, within the decentralized structure of the QDR network, some modules are more resilient than others. In conclusion, our work sheds light on the complexity of QDR and provides comprehensive understanding of a QDR immune network.


Assuntos
Resistência à Doença/imunologia , Suscetibilidade a Doenças/imunologia , Interações Hospedeiro-Patógeno , Imunomodulação , Modelos Biológicos , Doenças das Plantas/etiologia , Imunidade Vegetal , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Fenótipo , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Transcriptoma
16.
PLoS One ; 15(7): e0235018, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673321

RESUMO

Common scab disease in potato has become a widespread issue in major potato production areas, leading to increasing economic losses. Varietal resistance is seen as a viable and long-term scab management strategy. However, the genes and mechanisms of varietal resistance are unknown. In the current study, a comparative RNA transcriptome sequencing and differential gene signaling and priming sensitization studies were conducted in two potato cultivars that differ by their response to common scab (Streptomyces scabies), for unraveling the genes and pathways potentially involved in resistance within this pathosystem. We report on a consistent and contrasted gene expression pattern from 1,064 annotated genes differentiating a resistant (Hindenburg) and a susceptible (Green Mountain) cultivars, and identified a set of 273 co-regulated differentially expressed genes in 34 pathways that more likely reflect the genetic differences of the cultivars and metabolic mechanisms involved in the scab pathogenesis and resistance. The data suggest that comparative transcriptomic phenotyping can be used to predict scab lesion phenotype in breeding lines using mature potato tuber. The study also showed that the resistant cultivar, Hindenburg, has developed and maintained a capacity to sense and prime itself for persistent response to scab disease over time, and suggests an immune priming reaction as a mechanism for induced-resistance in scab resistant potato cultivars. The set of genes identified, described, and discussed in the study paves the foundation for detailed characterizations towards tailoring and designing procedures for targeted gene knockout through gene editing and phenotypic evaluation.


Assuntos
Perfilação da Expressão Gênica , Solanum tuberosum/imunologia , Streptomyces/imunologia , Resistência à Doença/genética , Resistência à Doença/imunologia , Suscetibilidade a Doenças/imunologia , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/imunologia , Escabiose/microbiologia , Solanum tuberosum/microbiologia , Especificidade da Espécie , Streptomyces/patogenicidade
17.
An. pediatr. (2003. Ed. impr.) ; 93(1): 60.e1-60.e7, jul. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-189679

RESUMO

El nuevo coronavirus (SARS-CoV-2) productor de síndrome respiratorio agudo severo surge en Wuhan, China, en diciembre de 2019. Genera la denominada enfermedad por coronavirus 2019 (COVID-19) y ha llevado a la declaración de emergencia de salud pública global a la Organización Mundial de la Salud. Este nuevo virus SARS-CoV-2 podría compartir características y respuesta inmune a las descritas para otros coronavirus. Dada su actividad sobre la vía del interferón y el modo en el que disregula la inmunidad innata, el uso de tratamientos dirigidos a modular o contener esta pueden ser de interés. Se realiza una revisión narrativa de la evidencia actual acerca de la inmunidad sobre coronavirus y su aplicabilidad para SARS-CoV-2. Se describe también la fisiopatogenia y la actividad leucocitaria subyacente, con intención de clarificar la posible utilidad de biomarcadores inflamatorios y el desarrollo de tratamientos personalizados


The new coronavirus (SARS-CoV-2) that causes a severe acute respiratory syndrome emerges in Wuhan, China, in December 2019. It produces the aforementioned disease due to coronavirus 2019 (COVID-19), and has led to a declaration of a world public health emergency by the World Health Organisation. This new SARS-CoV-2 virus could share characteristics and an immune response similar to those described for other coronavirus. Given its activity on the interferon pathway, and the manner in which it dysregulates innate immunity, the use of treatments directed at modulating or containing this could be of interest. A narrative review was made of the current evidence about immunity against coronavirus and its applicability to SARS-CoV-2. The physiopathogenesis is also described, along with the underlying leucocyte activity, with the intention of clarifying the possible usefulness of inflammatory biomarkers and the development of personalised treatments


Assuntos
Humanos , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Betacoronavirus/imunologia , Pandemias , Resistência à Doença/imunologia , Imunidade Inata/imunologia
18.
FASEB J ; 34(7): 8787-8795, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32525600

RESUMO

The dynamics, such as transmission, spatial epidemiology, and clinical course of Coronavirus Disease-2019 (COVID-19) have emerged as the most intriguing features and remain incompletely understood. The genetic landscape of an individual in particular, and a population in general seems to play a pivotal role in shaping the above COVID-19 dynamics. Considering the implications of host genes in the entry and replication of SARS-CoV-2 and in mounting the host immune response, it appears that multiple genes might be crucially involved in the above processes. Herein, we propose three potentially important genetic gateways to COVID-19 infection; these could explain at least in part the discrepancies of its spread, severity, and mortality. The variations within Angiotensin-converting enzyme 2 (ACE2) gene might constitute the first genetic gateway, influencing the spatial transmission dynamics of COVID-19. The Human Leukocyte Antigen locus, a master regulator of immunity against infection seems to be crucial in influencing susceptibility and severity of COVID-19 and can be the second genetic gateway. The genes regulating Toll-like receptor and complement pathways and subsequently cytokine storm induced exaggerated inflammatory pathways seem to underlie the severity of COVID-19, and such genes might represent the third genetic gateway. Host-pathogen interaction is a complex event and some additional genes might also contribute to the dynamics of COVID-19. Overall, these three genetic gateways proposed here might be the critical host determinants governing the risk, severity, and outcome of COVID-19. Genetic variations within these gateways could be key in influencing geographical discrepancies of COVID-19.


Assuntos
Betacoronavirus/fisiologia , Ativação do Complemento/genética , Infecções por Coronavirus/genética , Antígenos HLA/genética , Interações Hospedeiro-Patógeno/genética , Pandemias , Peptidil Dipeptidase A/genética , Pneumonia Viral/genética , Receptores Virais/genética , Receptores Toll-Like/genética , Grupos de Populações Continentais/genética , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/transmissão , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/genética , Resistência à Doença/imunologia , Predisposição Genética para Doença , Variação Genética , Antígenos HLA/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inflamação , Metagenômica , Mutação de Sentido Incorreto , Peptidil Dipeptidase A/fisiologia , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/transmissão , Prognóstico , Locos de Características Quantitativas , Receptores Virais/fisiologia , Risco , Receptores Toll-Like/imunologia , Resultado do Tratamento
19.
Sci Rep ; 10(1): 7765, 2020 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-32385321

RESUMO

The rise of anthelmintic resistance worldwide has led to the development of alternative control strategies for gastrointestinal nematodes (GIN) infections, which are one of the main constraints on the health of grazing small ruminants. Presently, breeding schemes rely mainly on fecal egg count (FEC) measurements on infected animals which are time-consuming and requires expertise in parasitology. Identifying and understanding the role of immunoglobulins in the mechanisms of resistance could provide a more efficient and sustainable method of identifying nematode-resistant animals for selection. In this study we review the findings on immunoglobulin response to GIN in the literature published to date (june 2019) and discuss the potential to use immunoglobulins as biomarkers. The literature review revealed 41 studies which measured at least one immunoglobulin: 35 focused on lamb immune response (18 used non-naïve lambs) and 7 on yearlings. In this review we propose a conceptual model summarizing the role of immunoglobulins in resistance to GIN. We highlight the need for more carefully designed and documented studies to allow comparisons across different populations on the immunoglobulin response to GIN infection.


Assuntos
Biomarcadores , Resistência à Doença/imunologia , Gastroenteropatias/imunologia , Gastroenteropatias/parasitologia , Imunoglobulinas/imunologia , Infecções por Nematoides/imunologia , Infecções por Nematoides/parasitologia , Animais , Cabras , Isotipos de Imunoglobulinas/imunologia , Ruminantes , Ovinos
20.
Aquat Toxicol ; 224: 105494, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32422488

RESUMO

Little is known about the impacts of dietary exposure to inorganic mercury (Hg) for a long duration on the health indicators, growth, and disease resistance in Oreochromis niloticus. Accordingly, the current study was designed to assess the effects of Hg contaminated diets on blood biochemistry, growth, chemical composition, Hg bioaccumulation in the tissues, histopathology of liver and head kidneys, and disease resistance to Aeromonas hydrophila of O. niloticus. Also, the efficiency of citronella oil, geranium oil (GO), curcumin (CUR), Bacillus toyonensis (BT), and Bacillus subtilis (BS) as dietary supplements on reversing the negative impacts of Hg were assessed. A total of 240 tilapia fingerlings were assigned to eight dietary treatments fed on the basal diet (G1), G1 diet contaminated with 50 ppm Hg (G2), whereas the other groups fed the G2 diet and enriched with 400 mg CO (G3), 400 mg GO (G4), 200 mg CUR (G5), 7 × 107 cells BT (G6), 7 × 107 cells BS (G7), and 7 × 107 BT + BS/ kg diet (G8) for 16 weeks. The obtained results showed that fish fed on the G2 diet had significantly impaired growth performance indicators, blood parameters, and resistance to bacterial infection compared with fish in the control group. Additionally, distinct pathological perturbations in liver and head kidneys were observed. In contrast, fish groups G3 to G8 had a significant enhancement in the growth performance, Hg bioaccumulation in fish tissues, blood biochemistry, and resistance against A. hydrophila infection compared with fish in the G2 group. Maximum improvement was recorded in G5, G6, and G8. Conclusively, from both health and an economic point of view, these results suggested that several benefits might be gained by adding these additives, especially CUR, BT, and BT + BS, on growth enhancement and ameliorating Hg negative impacts in O. niloticus.


Assuntos
Ração Animal/análise , Bioacumulação , Ciclídeos/crescimento & desenvolvimento , Resistência à Doença/efeitos dos fármacos , Doenças dos Peixes/prevenção & controle , Infecções por Bactérias Gram-Negativas/veterinária , Mercúrio/toxicidade , Poluentes Químicos da Água/toxicidade , Aeromonas hydrophila/patogenicidade , Animais , Ciclídeos/imunologia , Ciclídeos/microbiologia , Dieta , Suplementos Nutricionais , Resistência à Doença/imunologia , Doenças dos Peixes/imunologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/microbiologia , Rim Cefálico/efeitos dos fármacos , Rim Cefálico/metabolismo , Rim Cefálico/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Mercúrio/metabolismo , Poluentes Químicos da Água/metabolismo
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