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1.
Eur Rev Med Pharmacol Sci ; 24(16): 8606-8620, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32894568

RESUMO

OBJECTIVE: COVID-19 immune syndrome is a multi-systemic disorder induced by the COVID-19 infection. Pathobiological transitions and clinical stages of the COVID-19 syndrome following the attack of SARS-CoV-2 on the human body have not been fully explored. The aim of this review is to outline the three critical prominent phase regarding the clinicogenomics course of the COVID-19 immune syndrome. MATERIALS AND METHODS: In the clinical setting, the COVID-19 process presents as "asymptomatic/pre-symptomatic phase", "respiratory phase with mild/moderate/severe symptoms" and "multi-systemic clinical syndrome with impaired/disproportionate and/or defective immunity". The corresponding three genomic phases include the "ACE2, ANPEP transcripts in the initial phase", "EGFR and IGF2R transcripts in the propagating phase" and the "immune system related critical gene involvements of the complicating phase". RESULTS: The separation of the phases is important since the genomic features of each phase are different from each other and these different mechanisms lead to distinct clinical multi-systemic features. Comprehensive genomic profiling with next generation sequencing may play an important role in defining and clarifying these three unique separate phases for COVID-19. From our point of view, it is important to understand these unique phases of the syndrome in order to approach a COVID-19 patient bedside. CONCLUSIONS: This three-phase approach may be useful for future studies which will focus on the clinical management and development of the vaccines and/or specific drugs targeting the COVID-19 processes. ANPEP gene pathway may have a potential for the vaccine development. Regarding the specific disease treatments, MAS agonists, TXA127, Angiotensin (1-7) and soluble ACE2 could have therapeutic potential for the COVID-19 course. Moreover, future CRISPR technology can be utilized for the genomic editing and future management of the clinical course of the syndrome.


Assuntos
Doenças Assintomáticas , Infecções por Coronavirus/patologia , Sistema Imunitário/metabolismo , Pneumonia Viral/patologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Regulação da Expressão Gênica , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/patologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia , Prognóstico , Receptor IGF Tipo 2/genética , Receptor IGF Tipo 2/metabolismo , Sepse/complicações , Sepse/patologia , Índice de Gravidade de Doença , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo
2.
PLoS One ; 15(9): e0238044, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32997665

RESUMO

INTRODUCTION: Studies report that intense physical activity influences the down-regulation of immune function in athletes as well as the interaction between adipose tissue and the immune system. AIM: This study aimed to compare the plasma soluble levels of the immune checkpoint HLA-G (sHLA-G) molecule with the fat mass and muscle mass index among 77 bodybuilders and 64 controls. RESULTS: The comparisons of the percentage of body fat (%BF) revealed that the groups of male and female bodybuilders showed a statistically significant reduction in the percentage of body fat when compared to their control group, (P <0.0001, for both comparisons). Regarding sHLA-G levels, the comparisons showed that the group of male bodybuilders had significantly higher sHLA-G levels compared to the group of female bodybuilders (P = 0.0011). CONCLUSION: Our results showed that in bodybuilders with less body fat, the systemic levels of soluble HLA-G, an immunological molecule with recognized immunosuppressive function, are significantly higher and suggest that this immune mechanism may corroborate the immunosuppressive state in athletes undergoing intense and prolonged physical training.


Assuntos
Tecido Adiposo/metabolismo , Biomarcadores/sangue , Exercício Físico , Antígenos HLA-G/sangue , Sistema Imunitário/metabolismo , Levantamento de Peso/estatística & dados numéricos , Tecido Adiposo/imunologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Sistema Imunitário/imunologia , Masculino , Adulto Jovem
3.
Front Immunol ; 11: 1582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32793223

RESUMO

Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro- and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.


Assuntos
Diabetes Mellitus Tipo 2/imunologia , Diabetes Mellitus Tipo 2/patologia , Hiperglicemia/imunologia , Síndrome Metabólica/imunologia , Obesidade/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Suscetibilidade a Doenças/imunologia , Disbiose/imunologia , Microbioma Gastrointestinal , Humanos , Sistema Imunitário/metabolismo , Inflamação/imunologia , Estresse Oxidativo/imunologia , Pandemias , Pneumonia Viral/imunologia
4.
BMC Bioinformatics ; 21(1): 346, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778050

RESUMO

BACKGROUND: While technological advances have made it possible to profile the immune system at high resolution, translating high-throughput data into knowledge of immune mechanisms has been challenged by the complexity of the interactions underlying immune processes. Tools to explore the immune network are critical for better understanding the multi-layered processes that underlie immune function and dysfunction, but require a standardized network map of immune interactions. To facilitate this we have developed ImmunoGlobe, a manually curated intercellular immune interaction network extracted from Janeway's Immunobiology textbook. RESULTS: ImmunoGlobe is the first graphical representation of the immune interactome, and is comprised of 253 immune system components and 1112 unique immune interactions with detailed functional and characteristic annotations. Analysis of this network shows that it recapitulates known features of the human immune system and can be used uncover novel multi-step immune pathways, examine species-specific differences in immune processes, and predict the response of immune cells to stimuli. ImmunoGlobe is publicly available through a user-friendly interface at www.immunoglobe.org and can be downloaded as a computable graph and network table. CONCLUSION: While the fields of proteomics and genomics have long benefited from network analysis tools, no such tool yet exists for immunology. ImmunoGlobe provides a ground truth immune interaction network upon which such tools can be built. These tools will allow us to predict the outcome of complex immune interactions, providing mechanistic insight that allows us to precisely modulate immune responses in health and disease.


Assuntos
Comunicação Celular , Curadoria de Dados , Espaço Extracelular/metabolismo , Sistema Imunitário/metabolismo , Mapas de Interação de Proteínas , Software , Biologia de Sistemas , Animais , Humanos , Camundongos , Modelos Imunológicos
5.
BMB Rep ; 53(8): 400-412, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32731913

RESUMO

The world has witnessed unimaginable damage from the coronavirus disease-19 (COVID-19) pandemic. Because the pandemic is growing rapidly, it is important to consider diverse treatment options to effectively treat people worldwide. Since the immune system is at the hub of the infection, it is essential to regulate the dynamic balance in order to prevent the overexaggerated immune responses that subsequently result in multiorgan damage. The use of stem cells as treatment options has gained tremendous momentum in the past decade. The revolutionary measures in science have brought to the world mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-Exo) as therapeutic opportunities for various diseases. The MSCs and MSCExos have immunomodulatory functions; they can be used as therapy to strike a balance in the immune cells of patients with COVID-19. In this review, we discuss the basics of the cytokine storm in COVID-19, MSCs, and MSC-derived exosomes and the potential and stem-cell-based ongoing clinical trials for COVID-19. [BMB Reports 2020; 53(8): 400-412].


Assuntos
Infecções por Coronavirus/terapia , Exossomos/transplante , Transplante de Células-Tronco Mesenquimais , Pneumonia Viral/terapia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Citocinas/metabolismo , Humanos , Sistema Imunitário/metabolismo , Imunomodulação , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia
6.
Int J Mol Sci ; 21(15)2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32752138

RESUMO

The COVID-19 pandemic caused by the SARS-CoV-2 virus, overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined three independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cigs led to upregulation of pro-inflammatory cytokines and inflammasome-related genes. Specifically, chemokines including CCL20 and CXCL8 are upregulated in smokers, and CCL5 and CCR1 are upregulated in flavor/nicotine-containing e-cig users. We also found genes implicated in inflammasomes, such as CXCL1, CXCL2, NOD2, and ASC, to be upregulated in smokers and these e-cig users. Vaping flavor and nicotine-less e-cigs, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping may critically exacerbate COVID-19-related inflammation or increase susceptibility to COVID-19.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Sistema Imunitário/metabolismo , Peptidil Dipeptidase A/metabolismo , Fumar Tabaco , Adulto , Betacoronavirus/isolamento & purificação , Brônquios/citologia , Quimiocina CCL20/genética , Quimiocina CCL20/metabolismo , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Pessoa de Meia-Idade , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Pandemias , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Regulação para Cima , Adulto Jovem
7.
Life Sci ; 257: 118109, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32698072

RESUMO

Rheumatoid arthritis is an inflammatory autoimmune disease, characterized by synovial proliferation, destruction to articular cartilage and severe pain. The cannabinoids obtained from Cannabis sativa exhibited their actions via cannabinoid-1 and -2 receptors, which also provides a platform for endocannabinoids to act. The endocannabinoid system comprises endocannabinoid molecules involved in signaling processes, along with G-protein coupled receptors and enzymes associated with ligand biosynthesis, activation and degradation. The action of endocannabinoid system in immune system regulation, via primary CB2 activation, followed by inhibition of production of pro-inflammatory cytokines, auto-antibodies and MMPs, FLSs proliferation and T-cell mediated immune response, are elaborated as potential therapeutic regimes in rheumatoid arthritis. The involvement of endocannabinoid system in immune cells like, B cells, T cells and macrophages, as well as regulatory actions on sensory noniceptors to ameliorate pain is significantly highlighted in the review, elaborating the actions of endocannabinoid signaling in mitigating the disease events. The review also focuses on enhancement of endocannabinoid tone, either by inhibiting the degradation enzymes, like FAAH, MAGL, COX, CytP450, LOX, etc. or by retarding cellular uptake processes. Moreover, the review portrays the optimizing role of endocannabinoid system, in abbreviating the symptoms and complications of rheumatoid arthritis in patients and mitigating inflammation, pain and immune mediated effects significantly.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Endocanabinoides/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Artrite Reumatoide/metabolismo , Endocanabinoides/antagonistas & inibidores , Humanos , Sistema Imunitário/metabolismo , Inflamação/metabolismo , Receptor CB2 de Canabinoide/antagonistas & inibidores , Receptor CB2 de Canabinoide/metabolismo
8.
Arterioscler Thromb Vasc Biol ; 40(9): 1990-2001, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32698683

RESUMO

Innate and adaptive immunity participate in and regulate numerous human diseases. Increasing evidence implies that metabolic reprogramming mediates immune cell functional changes during immune responses. In this review, we present and discuss our current understanding of metabolic regulation in different immune cells and their subsets in response to pathological stimuli. An interactive biochemical and molecular model was established to characterize metabolic reprogramming and their functional implication in anti-inflammatory, immune resolution, and proinflammatory responses. We summarize 2 major features of metabolic reprogramming in inflammatory stages in innate and adaptive immune cells: (1) energy production and biosynthesis reprogramming, including increased glycolysis and decreased oxidative phosphorylation, to secure faster ATP production and biosynthesis for defense response and damage repair and (2) epigenetic reprogramming, including enhanced histone acetylation and suppressed DNA methylation, due to altered accessibility of acetyl/methyl group donor and metabolite-modulated enzymatic activity. Finally, we discuss current strategies of metabolic and epigenetic therapy in cardiovascular disease and recommend cell-specific metabolic and gene-targeted site-specific epigenetic alterations for future therapies.


Assuntos
Imunidade Adaptativa , Reprogramação Celular , Metabolismo Energético , Sistema Imunitário/metabolismo , Imunidade Inata , Mediadores da Inflamação/metabolismo , Inflamação/metabolismo , Animais , Epigênese Genética , Humanos , Sistema Imunitário/imunologia , Inflamação/genética , Inflamação/imunologia , Transdução de Sinais
11.
Nat Commun ; 11(1): 2213, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32371927

RESUMO

Despite infiltrating immune cells having an essential function in human disease and patients' responses to treatments, mechanisms influencing variability in infiltration patterns remain unclear. Here, using bulk RNA-seq data from 46 tissues in the Genotype-Tissue Expression project, we apply cell-type deconvolution algorithms to evaluate the immune landscape across the healthy human body. We discover that 49 of 189 infiltration-related phenotypes are associated with either age or sex (FDR < 0.1). Genetic analyses further show that 31 infiltration-related phenotypes have genome-wide significant associations (iQTLs) (P < 5.0 × 10-8), with a significant enrichment of same-tissue expression quantitative trait loci in suggested iQTLs (P < 10-5). Furthermore, we find an association between helper T cell content in thyroid tissue and a COMMD3/DNAJC1 regulatory variant (P = 7.5 × 10-10), which is associated with thyroiditis in other cohorts. Together, our results identify key factors influencing inter-individual variability of immune infiltration, to provide insights on potential therapeutic targets.


Assuntos
Perfilação da Expressão Gênica/métodos , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Sistema Imunitário/metabolismo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Adulto , Algoritmos , Feminino , Redes Reguladoras de Genes/genética , Redes Reguladoras de Genes/imunologia , Genótipo , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/imunologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo , Glândula Tireoide/citologia , Glândula Tireoide/imunologia , Glândula Tireoide/metabolismo
12.
PLoS One ; 15(5): e0233543, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32469933

RESUMO

Genome-wide transcriptomic analyses have provided valuable insight into fundamental biology and disease pathophysiology. Many studies have taken advantage of the correlation in the expression patterns of the transcriptome to infer a potential biologic function of uncharacterized genes, and multiple groups have examined the relationship between co-expression, co-regulation, and gene function on a broader scale. Given the unique characteristics of immune cells circulating in the blood, we were interested in determining whether it was possible to identify functional co-expression modules in human immune cells. Specifically, we sequenced the transcriptome of nine immune cell types from peripheral blood cells of healthy donors and, using a combination of global and targeted analyses of genes within co-expression modules, we were able to determine functions for these modules that were cell lineage-specific or shared among multiple cell lineages. In addition, our analyses identified transcription factors likely important for immune cell lineage commitment and/or maintenance.


Assuntos
Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Sistema Imunitário/metabolismo , Leucócitos Mononucleares/metabolismo , Adulto , Linhagem da Célula , Hematopoese , Humanos , Sistema Imunitário/citologia , Leucócitos Mononucleares/fisiologia , Masculino , Análise de Sequência de RNA , Fatores de Transcrição
14.
J Vis Exp ; (157)2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32202530

RESUMO

The growing use of medical devices (e.g., vascular grafts, stents, and cardiac catheters) for temporary or permanent purposes that remain in the body's circulatory system demands a reliable and multiparametric approach that evaluates the possible hematologic complications caused by these devices (i.e., activation and destruction of blood components). Comprehensive in vitro hemocompatibility testing of blood-contacting implants is the first step towards successful in vivo implementation. Therefore, extensive analysis according to the International Organization for Standardization 10993-4 (ISO 10993-4) is mandatory prior to clinical application. The presented flow loop describes a sensitive model to analyze the hemostatic performance of stents (in this case, neurovascular) and reveal adverse effects. The use of fresh human whole blood and gentle blood sampling are essential to avoid the preactivation of blood. The blood is perfused through a heparinized tubing containing the test specimen by using a peristaltic pump at a rate of 150 mL/min at 37 °C for 60 min. Before and after perfusion, hematologic markers (i.e., blood cell count, hemoglobin, hematocrit, and plasmatic markers) indicating the activation of leukocytes (polymorphonuclear [PMN]-elastase), platelets (ß-thromboglobulin [ß-TG]), the coagulation system (thombin-antithrombin III [TAT]), and the complement cascade (SC5b-9) are analyzed. In conclusion, we present an essential and reliable model for extensive hemocompatibility testing of stents and other blood-contacting devices prior to clinical application.


Assuntos
Circulação Sanguínea/fisiologia , Prótese Vascular , Teste de Materiais/métodos , Modelos Biológicos , Biomarcadores/metabolismo , Contagem de Células Sanguíneas , Circulação Sanguínea/efeitos dos fármacos , Coleta de Amostras Sanguíneas , Proteínas do Sistema Complemento/metabolismo , Heparina/farmacologia , Humanos , Sistema Imunitário/metabolismo , Elastase Pancreática/metabolismo , Plasma , Stents , beta-Tromboglobulina/metabolismo
15.
PLoS Genet ; 16(3): e1008686, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32168362

RESUMO

Identifying the factors that shape protein expression variability in complex multi-cellular organisms has primarily focused on promoter architecture and regulation of single-cell expression in cis. However, this targeted approach has to date been unable to identify major regulators of cell-to-cell gene expression variability in humans. To address this, we have combined single-cell protein expression measurements in the human immune system using flow cytometry with a quantitative genetics analysis. For the majority of proteins whose variability in expression has a heritable component, we find that genetic variants act in trans, with notably fewer variants acting in cis. Furthermore, we highlight using Mendelian Randomization that these variability-Quantitative Trait Loci might be driven by the cis regulation of upstream genes. This indicates that natural selection may balance the impact of gene regulation in cis with downstream impacts on expression variability in trans.


Assuntos
Regulação da Expressão Gênica/genética , Expressão Gênica/genética , Alelos , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica/métodos , Testes Genéticos/métodos , Estudo de Associação Genômica Ampla/métodos , Humanos , Sistema Imunitário/metabolismo , Imunidade/genética , Masculino , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Seleção Genética/genética
16.
Immunity ; 52(3): 464-474, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32187517

RESUMO

The ability of the nervous system to sense environmental stimuli and to relay these signals to immune cells via neurotransmitters and neuropeptides is indispensable for effective immunity and tissue homeostasis. Depending on the tissue microenvironment and distinct drivers of a certain immune response, the same neuronal populations and neuro-mediators can exert opposing effects, promoting or inhibiting tissue immunity. Here, we review the current understanding of the mechanisms that underlie the complex interactions between the immune and the nervous systems in different tissues and contexts. We outline current gaps in knowledge and argue for the importance of considering infectious and inflammatory disease within a conceptual framework that integrates neuro-immune circuits both local and systemic, so as to better understand effective immunity to develop improved approaches to treat inflammation and disease.


Assuntos
Sistema Imunitário/imunologia , Sistema Nervoso/imunologia , Neuroimunomodulação/imunologia , Neurônios/imunologia , Animais , Humanos , Sistema Imunitário/citologia , Sistema Imunitário/metabolismo , Imunidade Inata/imunologia , Sistema Nervoso/citologia , Sistema Nervoso/metabolismo , Inflamação Neurogênica/imunologia , Inflamação Neurogênica/metabolismo , Neurônios/metabolismo , Neuropeptídeos/imunologia , Neuropeptídeos/metabolismo , Transdução de Sinais/imunologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-32208989

RESUMO

Tryptophan catabolism through the kynurenine pathway generates a variety of bioactive metabolites. Physical exercise can modulate kynurenine pathway metabolism in skeletal muscle and thus change the concentrations of select compounds in peripheral tissues and in the central nervous system. Here we review recent advances in our understanding of how exercise alters tryptophan-kynurenine metabolism in muscle and its subsequent local and distal effects. We propose that the effects of kynurenine pathway metabolites on skeletal muscle, adipose tissue, immune system, and the brain suggest that some of these compounds could qualify as exercise-induced myokines. Indeed, some of the more recently discovered biological activities for kynurenines include many of the best-known benefits of exercise: improved energy homeostasis, promotion of an anti-inflammatory environment, and neuroprotection. Finally, by considering the tissue expression of the different membrane and cytosolic receptors for kynurenines, we discuss known and potential biological activities for these tryptophan metabolites.


Assuntos
Sistema Nervoso Central/metabolismo , Cinurenina/metabolismo , Redes e Vias Metabólicas/fisiologia , Músculo Esquelético/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiologia , Sistema Nervoso Central/fisiologia , Exercício Físico/fisiologia , Homeostase/genética , Homeostase/fisiologia , Humanos , Sistema Imunitário/metabolismo , Sistema Imunitário/fisiologia , Cinurenina/genética , Metabolismo/fisiologia , Músculo Esquelético/fisiologia , PPAR gama/genética , Triptofano/metabolismo
18.
Nat Rev Immunol ; 20(6): 375-388, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32132681

RESUMO

Immune memory is a defining feature of the acquired immune system, but activation of the innate immune system can also result in enhanced responsiveness to subsequent triggers. This process has been termed 'trained immunity', a de facto innate immune memory. Research in the past decade has pointed to the broad benefits of trained immunity for host defence but has also suggested potentially detrimental outcomes in immune-mediated and chronic inflammatory diseases. Here we define 'trained immunity' as a biological process and discuss the innate stimuli and the epigenetic and metabolic reprogramming events that shape the induction of trained immunity.


Assuntos
Imunidade Adaptativa/imunologia , Epigênese Genética/imunologia , Doenças do Sistema Imunitário/imunologia , Sistema Imunitário/imunologia , Imunidade Inata/imunologia , Memória Imunológica/imunologia , Imunidade Adaptativa/genética , Animais , Humanos , Sistema Imunitário/metabolismo , Doenças do Sistema Imunitário/genética , Tolerância Imunológica/genética , Tolerância Imunológica/imunologia , Imunidade Inata/genética , Memória Imunológica/genética , Inflamação/genética , Inflamação/imunologia
19.
PLoS One ; 15(3): e0230021, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32160226

RESUMO

Supplementing chicken feed with antibiotics can improve survival and prevent disease outbreaks. However, overuse of antibiotics may promote the development of antibiotic-resistant bacteria. Recently, antimicrobial peptides have been proposed as alternatives to antibiotics in animal husbandry. Here, we evaluate the effects of antimicrobial peptide, Epinephelus lanceolatus piscidin (EP), in Gallus gallus domesticus. The gene encoding EP was isolated, sequenced, codon-optimized and cloned into a Pichia pastoris recombinant protein expression system. The expressed recombinant EP (rEP) was then used as a dietary supplement for G. g. domesticus; overall health, growth performance and immunity were assessed. Supernatant from rEP-expressing yeast showed in vitro antimicrobial activity against Gram-positive and Gram-negative bacteria, according to an inhibition-zone diameter (mm) assay. Moreover, the antimicrobial peptide function of rEP was temperature independent. The fermentation broth yielded a spray-dried powder formulation containing 262.9 µg EP/g powder, and LC-MS/MS (tandem MS) analysis confirmed that rEP had a molecular weight of 4279 Da, as expected for the 34-amino acid peptide; the DNA sequence of the expression vector was also validated. We then evaluated rEP as a feed additive for G. g. domesticus. Treatment groups included control, basal diet and rEP at different doses (0.75, 1.5, 3.0, 6.0 and 12%). Compared to control, rEP supplementation increased G. g. domesticus weight gain, feed efficiency, IL-10 and IFN-γ production. Our results suggest that crude rEP could provide an alternative to traditional antibiotic feed additives for G. g. domesticus, serving to enhance growth and health of the animals.


Assuntos
Peptídeos Catiônicos Antimicrobianos/metabolismo , Galinhas/imunologia , Sistema Imunitário/metabolismo , Perciformes/metabolismo , Sequência de Aminoácidos , Animais , Anti-Infecciosos/análise , Anti-Infecciosos/metabolismo , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/análise , Peptídeos Catiônicos Antimicrobianos/classificação , Peptídeos Catiônicos Antimicrobianos/genética , Galinhas/crescimento & desenvolvimento , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Suplementos Nutricionais , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Sistema Imunitário/efeitos dos fármacos , Interferon gama/metabolismo , Interleucina-10/metabolismo , Filogenia , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Alinhamento de Sequência , Espectrometria de Massas em Tandem , Temperatura
20.
Platelets ; 31(3): 315-321, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32054377

RESUMO

Diagnosis of immune thrombocytopenia (ITP) and prediction of response to therapy remain significant and constant challenges in hematology. In patients who present with ITP, the platelet count is frequently used as a surrogate marker for disease severity, and so often determines the need for therapy. Although there is a clear link between thrombocytopenia and hemostasis, a direct correlation between the extent of thrombocytopenia and bleeding symptoms, especially at lower platelet counts is lacking. Thus, bleeding in ITP is heterogeneous, unpredictable, and nearly always based on a multitude of risk factors, beyond the platelet count. The development of an evidence-based, validated risk stratification model for ITP treatment is a major goal in the ITP community and this review discusses new laboratory approaches to evaluate the various pathobiologies of ITP that may inform such a model.


Assuntos
Suscetibilidade a Doenças , Púrpura Trombocitopênica Idiopática/etiologia , Pesquisa/tendências , Animais , Biomarcadores , Plaquetas/imunologia , Plaquetas/metabolismo , Plaquetas/patologia , Suscetibilidade a Doenças/imunologia , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Megacariócitos/imunologia , Megacariócitos/metabolismo , Megacariócitos/patologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/metabolismo , Púrpura Trombocitopênica Idiopática/terapia
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