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1.
Molecules ; 26(12)2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34204601

RESUMO

Interferonopathies are rare genetic conditions defined by systemic inflammatory episodes caused by innate immune system activation in the absence of pathogens. Currently, no targeted drugs are authorized for clinical use in these diseases. In this work, we studied the contribution of sulforaphane (SFN), a cruciferous-derived bioactive molecule, in the modulation of interferon-driven inflammation in an immortalized human hepatocytes (IHH) line and in two healthy volunteers, focusing on STING, a key-component player in interferon pathway, interferon signature modulation, and GSTM1 expression and genotype, which contributes to SFN metabolism and excretion. In vitro, SFN exposure reduced STING expression as well as interferon signature in the presence of the pro-inflammatory stimulus cGAMP (cGAMP 3 h vs. SFN+cGAMP 3 h p value < 0.0001; cGAMP 6 h vs. SFN+cGAMP 6 h p < 0.001, one way ANOVA), restoring STING expression to the level of unstimulated cells. In preliminary experiments on healthy volunteers, no appreciable variations in interferon signature were identified after SFN assumption, while only in one of them, presenting the GSTM1 wild type genotype related to reduced SFN excretion, could a downregulation of STING be recorded. This study confirmed that SFN inhibits STING-mediated inflammation and interferon-stimulated genes expression in vitro. However, only a trend towards the downregulation of STING could be reproduced in vivo. Results obtained have to be confirmed in a larger group of healthy individuals and in patients with type I interferonopathies to define if the assumption of SFN could be useful as supportive therapy.


Assuntos
Inflamação/metabolismo , Isotiocianatos/farmacologia , Sulfóxidos/farmacologia , Adulto , Linhagem Celular Tumoral , Feminino , Expressão Gênica/efeitos dos fármacos , Genótipo , Glutationa Transferase/metabolismo , Voluntários Saudáveis , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Humanos , Imunidade Inata/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interferons/efeitos adversos , Interferons/genética , Interferons/farmacologia , Isotiocianatos/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Sulfóxidos/metabolismo
3.
Nutrients ; 13(5)2021 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-34063252

RESUMO

Innate immunity plays a determinant role in high fat diet (HFD)-induced insulin resistance. This study compares the effects of immunonutritional bioactives from Chenopodium quinoa (WQ) or Salvia hispanica L. (Ch) when used to partially replace wheat flour (WB) into bread formulations. These flours were chosen to condition starch and lipid content in the products as well as because their immunonutritional activity. To be administered with different bread formulations, HFD-fed C57BL/6J mice were distributed in different groups: (i) wild type, (ii) displaying inherited disturbances in glucose homeostasis, and (iii) displaying dietary iron-mediated impairment of the innate immune TLR4/TRAM/TRIF pathway. We analyze the effects of the products on glycaemia and insulin resistance (HOMA-IR), plasmatic triglycerides, intestinal and hepatic gene expression and variations of myeloid (MY), and lymphoid (LY) cells population in peripheral blood. Our results show that feeding animals with WQ and Ch formulations influenced the expression of lipogenic and coronary risk markers, thus attaining a better control of hepatic lipid accumulation. WQ and Ch products also improved glucose homeostasis compared to WB, normalizing the HOMA-IR in animals with an altered glucose and lipid metabolism. These positive effects were associated with positive variations in the peripheral myeloid cells population.


Assuntos
Chenopodium quinoa , Farinha , Resistência à Insulina/fisiologia , Células Mieloides/efeitos dos fármacos , Compostos Fitoquímicos/administração & dosagem , Salvia , Animais , Glicemia/imunologia , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Imunidade Inata/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Linfócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Fenômenos Fisiológicos da Nutrição/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição/imunologia , Triglicerídeos/sangue
4.
Fish Shellfish Immunol ; 115: 124-133, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34077788

RESUMO

Aquaculture is one of the important globally growing industries. It serves as an important food source of protein for human beings. With the expanding demand for the fish and their products it has become extremely important to improve the aquaculture practices. Aquaculture in India has witnessed huge mortalities caused by bacteria, viruses, fungi, nematodes etc. Aquatic weeds plants are harmful for aquaculture in many ways. Present study is aimed to overcome the disease caused by Aeromonas hydrophila (fish pathogenic bacteria) through feed supplementation of two aquatic weed plants (Azolla pinnata and Ceratophyllum demersum). The fish were divided into 6 groups: experimental groups (fish fed on supplementary feed at 5% and 2.5% concentration for individual plant and challenged with bacteria), positive control (fish fed on non-supplemented feed and challenged with bacteria) and negative control (fish fed on non-supplementary feed and not challenged with bacteria). It was observed that supplemented feed enhanced both cell mediated and humoral immunity in fish. Therefore, we advocate that feed formulated with incorporation of Azolla pinnata and Ceratophyllum demersum leaf powder at 5% and 2.5% could be used to prevent disease caused by A. hydrophila or can be used to enhance fish health by boosting its immune system. The results of this study also showed an improved digestibility in fish fed on supplemented feed.


Assuntos
Imunidade Adaptativa/efeitos dos fármacos , Peixes-Gato/fisiologia , Sistema Digestório/efeitos dos fármacos , Gleiquênias/química , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/metabolismo , Magnoliopsida/química , Ração Animal/análise , Animais , Peixes-Gato/imunologia , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Fatores Imunológicos/administração & dosagem , Masculino , Polypodiaceae
5.
Fish Shellfish Immunol ; 115: 112-123, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34098068

RESUMO

Tachypleus amebocyte lysate (TAL) is crucial in medical testing, but its industry in China has been restricted due to the decline of horseshoe crab population in recent years. Exploring methods of enhancing immunity and rapid hemocytes proliferation is urgent for the industrial horseshoe crab culture. In this study, ß-glucan (G), peptidoglycan (P), and squalene (S) were injected to horseshoe crabs at two concentrations (5 and 10 mg/kg), in order to compare their effects on total hemocyte count (THC), reactive oxygen species (ROS), and non-specific immune enzyme activities. Results showed that the THC, superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC) were significantly increased by three immunostimulants at different points of time; ROS was significantly increased except at two squalene groups; lysozyme (LZM) and alkaline phosphatase (AKP) activity were increased except at low dose (5 mg/kg) squalene group; malondialdehyde (MDA) activity was decreased in all treatments; and hemocyanin concentration (HC) changed little during the experiment. At the 48th hour, THC, ROS, SOD, CAT, T-AOC, LZM, and AKP activities were significantly higher in the two peptidoglycan groups than those in the control group; the low dose ß-glucan and squalene groups showed significantly higher SOD and CAT, but their THC and AKP were not significantly different from those of the control group. In general, all three immunostimulants stimulated the hemolymph parameters of horseshoe crabs, notably, peptidoglycan could significantly increase the THC and enzyme activities, suggesting that peptidoglycan can be developed as an efficient immunostimulant for horseshoe crabs.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Hemócitos/efeitos dos fármacos , Caranguejos Ferradura/imunologia , Imunidade Inata/efeitos dos fármacos , Animais , Caranguejos Ferradura/efeitos dos fármacos , Masculino , Peptidoglicano/administração & dosagem , Esqualeno/administração & dosagem , beta-Glucanas/administração & dosagem
6.
Fish Shellfish Immunol ; 115: 212-220, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34146675

RESUMO

Eight weeks feeding experiment was managed to evaluate the impacts of dietary addition of pineapple peel powder (PAPP) and Lactobacillus plantarum CR1T5 (LP) individual or mixed on growth performance, skin mucus and serum immunities, as well as disease resistance of Nile tilapia. Fish (average weight 20.91 ± 0.11 g) were fed four diets: Diet 1 (0 g kg-1 PAPP and 0 CFU g-1 L. plantarum, Diet 2 (10 g kg-1 PAPP), Diet 3 (108 CFU g-1L. plantarum), and Diet 4 (10 g kg-1 PAPP + 108 CFU g-1L. plantarum). Serum and mucus immune responses, as well as growth rate, were assessed every 4 weeks. Ten fish were chosen for the challenge test with Streptococcus agalactiae after 8 weeks post-feeding. The findings showed that PAPP and/or LP diets increased (P ≤ 0.05) growth performance, skin mucus, and serum immune responses. The best data were obtained in fish fed a mixture of PAPP and LP. Nevertheless, no variation (P > 0.05) was recorded between groups fed PAPP or LP. The relative survival percentage (RSP, %) in Diet 2, Diet 3, and Diet 4 was 46.15%, 50.0%, and 73.08%. Fish fed mixture of PAPP + LP recorded the best (P < 0.05) survival rate versus other treatments. The current findings recommended using a mixture of PAPP and LP as promising functional additives for aquaculture practice.


Assuntos
Ananas/química , Ciclídeos/imunologia , Resistência à Doença , Imunidade Inata , Lactobacillus plantarum/química , Probióticos/metabolismo , Ração Animal/análise , Animais , Aquicultura , Ciclídeos/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Resistência à Doença/efeitos dos fármacos , Frutas/química , Imunidade Inata/efeitos dos fármacos , Pós/administração & dosagem , Pós/química , Probióticos/administração & dosagem , Distribuição Aleatória
7.
Mol Cells ; 44(6): 408-421, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34059561

RESUMO

The outbreak of coronavirus disease 2019 (COVID-19) has not only affected human health but also diverted the focus of research and derailed the world economy over the past year. Recently, vaccination against COVID-19 has begun, but further studies on effective therapeutic agents are still needed. The severity of COVID-19 is attributable to several factors such as the dysfunctional host immune response manifested by uncontrolled viral replication, type I interferon suppression, and release of impaired cytokines by the infected resident and recruited cells. Due to the evolving pathophysiology and direct involvement of the host immune system in COVID-19, the use of immune-modulating drugs is still challenging. For the use of immune-modulating drugs in severe COVID-19, it is important to balance the fight between the aggravated immune system and suppression of immune defense against the virus that causes secondary infection. In addition, the interplaying events that occur during virus-host interactions, such as activation of the host immune system, immune evasion mechanism of the virus, and manifestation of different stages of COVID-19, are disjunctive and require thorough streamlining. This review provides an update on the immunotherapeutic interventions implemented to combat COVID-19 along with the understanding of molecular aspects of the immune evasion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may provide opportunities to develop more effective and promising therapeutics.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , COVID-19/terapia , Evasão da Resposta Imune/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Replicação Viral/efeitos dos fármacos , COVID-19/imunologia , COVID-19/patologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Ensaios Clínicos como Assunto , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Dexametasona/uso terapêutico , Combinação de Medicamentos , Humanos , Imunidade Inata/efeitos dos fármacos , Imunização Passiva/métodos , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Peptídeos/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Replicação Viral/imunologia
8.
Asian Pac J Allergy Immunol ; 39(2): 69-77, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34174806

RESUMO

A novel severe acute respiratory syndrome COVID-19 caused by coronavirus SARS-CoV-2 has been confirmed to infect more than 100 million people globally, with mortality reaching nearly 3 million as of March 2021. The symptoms vary widely, from the absence of any symptoms to death. The severity of COVID-19 relates to hyperinflammatory conditions with acute respiratory distress syndrome (ARDS), which leads to multiple-organ failure and death. Innate immunity plays an important role in the early response to SARS-CoV-2 infection and regulates the pathogenesis and its clinical outcomes. The most severe cases of COVID-19 present with increased innate immune cell infiltration in the lung, and elevated pro-inflammatory cytokines in the blood serum that are associated with disease severity. Here we review the innate immune response to SARS-CoV-2 infection based on the recent reports and discuss the potential roles of innate immune cells and their mediators in pathogenesis that dictate the outcome of the disease. Understanding the roles of innate immune responses at the initial stages of infection may provide early windows into treatment and clues for vaccine development.


Assuntos
COVID-19/imunologia , Imunidade Inata , SARS-CoV-2/imunologia , Animais , Antivirais/uso terapêutico , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/virologia , Vacinas contra COVID-19/uso terapêutico , Citocinas/sangue , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença
9.
Mol Cells ; 44(6): 384-391, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34098591

RESUMO

The recent appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people around the world and caused a global pandemic of coronavirus disease 2019 (COVID-19). It has been suggested that uncontrolled, exaggerated inflammation contributes to the adverse outcomes of COVID-19. In this review, we summarize our current understanding of the innate immune response elicited by SARS-CoV-2 infection and the hyperinflammation that contributes to disease severity and death. We also discuss the immunological determinants behind COVID-19 severity and propose a rationale for the underlying mechanisms.


Assuntos
COVID-19/imunologia , Síndrome da Liberação de Citocina/imunologia , Interações Hospedeiro-Patógeno/imunologia , SARS-CoV-2/patogenicidade , Síndrome Respiratória Aguda Grave/imunologia , Anti-Inflamatórios/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/mortalidade , COVID-19/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/mortalidade , Síndrome da Liberação de Citocina/virologia , Dexametasona/uso terapêutico , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Imunidade Inata/efeitos dos fármacos , Inflamação , Interferon Tipo I/genética , Interferon Tipo I/imunologia , Interleucinas/genética , Interleucinas/imunologia , SARS-CoV-2/imunologia , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/mortalidade , Síndrome Respiratória Aguda Grave/virologia , Índice de Gravidade de Doença , Transdução de Sinais , Análise de Sobrevida
10.
Int J Mol Sci ; 22(9)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064508

RESUMO

During tumor growth, angiogenesis is required to ensure oxygen and nutrient transport to the tumor. Vascular endothelial growth factor (VEGF) is the major inducer of angiogenesis and appears to be a key modulator of the anti-tumor immune response. Indeed, VEGF modulates innate and adaptive immune responses through direct interactions and indirectly by modulating protein expressions on endothelial cells or vascular permeability. The inhibition of the VEGF signaling pathway is clinically approved for the treatment of several cancers. Therapies targeting VEGF can modulate the tumor vasculature and the immune response. In this review, we discuss the roles of VEGF in the anti-tumor immune response. In addition, we summarize therapeutic strategies based on its inhibition, and their clinical approval.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Fatores Imunológicos/uso terapêutico , Neoplasias/tratamento farmacológico , Neovascularização Patológica/prevenção & controle , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Imunidade Adaptativa/efeitos dos fármacos , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab/uso terapêutico , Permeabilidade Capilar/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Células Endoteliais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/patologia , Neovascularização Patológica/genética , Neovascularização Patológica/imunologia , Neovascularização Patológica/patologia , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Transdução de Sinais , Sorafenibe/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/imunologia
11.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34074061

RESUMO

BACKGROUND: Erythritol, a sugar alcohol, is widely used as a substitute for sugar in diets for patients with diabetes or obesity. METHODS: In this study, we aimed to investigate the effects of erythritol on metabolic disorders induced by a high-fat diet in C57BL/6J mice, while focusing on changes in innate immunity. RESULTS: Mice that were fed a high-fat diet and administered water containing 5% erythritol (Ery group) had markedly lower body weight, improved glucose tolerance, and markedly higher energy expenditure than the control mice (Ctrl group) (n = 6). Furthermore, compared with the Ctrl group, the Ery group had lesser fat deposition in the liver, smaller adipocytes, and significantly better inflammatory findings in the small intestine. The concentrations of short-chain fatty acids (SCFAs), such as acetic acid, propanoic acid, and butanoic acid, in the serum, feces, and white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. In flow cytometry experiments, group 3 innate lymphoid cell (ILC3) counts in the lamina propria of the small intestine and ILC2 counts in the white adipose tissue of the Ery group were markedly higher than those in the Ctrl group. Quantitative real-time reverse transcription polymerase chain reaction analyses showed that the Il-22 expression in the small intestine of the Ery group was markedly higher than that in the Ctrl group. CONCLUSIONS: Erythritol markedly decreased metabolic disorders such as diet-induced obesity, glucose intolerance, dyslipidemia, and fat accumulation in the mouse liver by increasing SCFAs and modulating innate immunity.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Eritritol/farmacologia , Intolerância à Glucose/dietoterapia , Imunidade Inata/efeitos dos fármacos , Intestino Delgado/efeitos dos fármacos , Obesidade/tratamento farmacológico , Adipócitos/citologia , Adipócitos/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo Branco/metabolismo , Animais , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Metabolismo Energético/efeitos dos fármacos , Eritritol/administração & dosagem , Ácidos Graxos Voláteis/sangue , Ácidos Graxos Voláteis/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Intolerância à Glucose/metabolismo , Imunidade Inata/genética , Inflamação/dietoterapia , Inflamação/genética , Inflamação/metabolismo , Interleucinas/genética , Interleucinas/metabolismo , Intestino Delgado/imunologia , Intestino Delgado/metabolismo , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Fígado/patologia , Linfócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Membrana Mucosa/efeitos dos fármacos , Membrana Mucosa/metabolismo , Obesidade/genética , Obesidade/metabolismo
12.
Fish Shellfish Immunol ; 114: 238-252, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33989765

RESUMO

The effect of Agaricus bisporus polysaccharides (ABPs) supplemented diet on growth rate, antioxidant capacity, innate-adaptive immune response, proinflammatory and antiinflammatory genes expression in Ctenopharyngodon idella against Aeromonas hydrophila is reported. In both normal and challenged groups fed with 1.0 and 1.5 mg kg-1 ABPs diets resulted in a significant weight gain and feed intake. The survival was 100% in normal fish fed without or with any ABPs diet; the challenged fish fed with 1.0 mg kg-1 ABPs diet had 98.6% survival. The RBC and WBC counts, Hb, and Hct levels were significant in both normal and challenged groups fed with 1.0 and 1.5 mg kg-1 ABPs diets. A significant increase in total protein and albumin level was observed in both groups fed with 1.0 and 1.5 mg kg-1 ABPs diets. Significant increase in GPx, ROS, GR, GSH, PC, and MnSOD activity was observed in HK of both groups fed with 1.0 and 1.5 mg kg-1 ABPs diets; similarly both groups when fed with the same ABPs diets showed significant Lz, C3, and C4 activity. However, both groups fed with 1.0 mg kg-1 ABPs diet showed significant ß-defensin, LEAP-2A, IL-6, and NF-κB P65 mRNA expression. Similarly, IFN-γ2, IL-10, and TNFα mRNA expressions were significant in both groups fed with 1.0 mg kg-1 ABPs diet. The results indicate that both normal and challenged C. idella fed with a 1.0 mg kg-1 ABPs diet had better growth, antioxidant status, immune response, and pro-anti-inflammatory gene modulation against A. hydrophila.


Assuntos
Agaricus/química , Ração Animal/análise , Carpas/metabolismo , Suplementos Nutricionais , Polissacarídeos/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Anti-Inflamatórios/metabolismo , Antioxidantes/metabolismo , Dieta/veterinária , Regulação da Expressão Gênica/efeitos dos fármacos , Imunidade Inata/efeitos dos fármacos , Polissacarídeos/química
13.
Front Immunol ; 12: 613056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936032

RESUMO

Multiple factors are involved in the process leading to melanocyte loss in vitiligo including environmental triggers, genetic polymorphisms, metabolic alterations, and autoimmunity. This review aims to highlight current knowledge on how danger signals released by stressed epidermal cells in a predisposed patient can trigger the innate immune system and initiate a cascade of events leading to an autoreactive immune response, ultimately contributing to melanocyte disappearance in vitiligo. We will explore the genetic data available, the specific role of damage-associated-molecular patterns, and pattern-recognition receptors, as well as the cellular players involved in the innate immune response. Finally, the relevance of therapeutic strategies targeting this pathway to improve this inflammatory and autoimmune condition is also discussed.


Assuntos
Imunidade Inata/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/imunologia , Estresse Fisiológico/efeitos dos fármacos , Vitiligo/etiologia , Animais , Biomarcadores , Terapia Combinada , Gerenciamento Clínico , Suscetibilidade a Doenças/imunologia , Predisposição Genética para Doença , Humanos , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Receptores de Reconhecimento de Padrão/metabolismo , Transdução de Sinais , Pele/patologia , Vitiligo/tratamento farmacológico , Vitiligo/metabolismo , Vitiligo/patologia
14.
Front Immunol ; 12: 607178, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959120

RESUMO

The spread of infectious diseases is rampant. The emergence of new infections, the irrational use of antibiotics in medicine and their widespread use in agriculture contribute to the emergence of microorganisms that are resistant to antimicrobial drugs. By 2050, mortality from antibiotic-resistant strains of bacteria is projected to increase up to 10 million people per year, which will exceed mortality from cancer. Mutations in bacteria and viruses are occurring faster than new drugs and vaccines are being introduced to the market. In search of effective protection against infections, new strategies and approaches are being developed, one of which is the use of innate immunity activators in combination with etiotropic chemotherapy drugs. Muramyl peptides, which are part of peptidoglycan of cell walls of all known bacteria, regularly formed in the body during the breakdown of microflora and considered to be natural regulators of immunity. Their interaction with intracellular receptors launches a sequence of processes that ultimately leads to the increased expression of genes of MHC molecules, pro-inflammatory mediators, cytokines and their soluble and membrane-associated receptors. As a result, all subpopulations of immunocompetent cells are activated: macrophages and dendritic cells, neutrophils, T-, B- lymphocytes and natural killer cells for an adequate response to foreign or transformed antigens, manifested both in the regulation of the inflammatory response and in providing immunological tolerance. Muramyl peptides take part in the process of hematopoiesis, stimulating production of colony-stimulating factors, which is the basis for their use in the treatment of oncological diseases. In this review we highlight clinical trials of drugs based on muramyl peptides, as well as clinical efficacy of drugs mifamurtide, lycopid, liasten and polimuramil. Such a multifactorial effect of muramyl peptides and a well-known mechanism of activity make them promising drugs in the treatment and preventing of infectious, allergic and oncological diseases, and in the composition of vaccines.


Assuntos
Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata/efeitos dos fármacos , Imunomodulação , Peptidoglicano/farmacologia , Animais , Ensaios Clínicos como Assunto , Desenvolvimento de Medicamentos , História do Século XX , História do Século XXI , Humanos , Monossacarídeos/química , Monossacarídeos/imunologia , Peptidoglicano/química , Peptidoglicano/imunologia , Peptidoglicano/uso terapêutico , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/imunologia , Polissacarídeos Bacterianos/farmacologia , Polissacarídeos Bacterianos/uso terapêutico , Pesquisa/história , Relação Estrutura-Atividade , Resultado do Tratamento
15.
Nat Immunol ; 22(7): 829-838, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33963333

RESUMO

The innate immune response is critical for recognizing and controlling infections through the release of cytokines and chemokines. However, severe pathology during some infections, including SARS-CoV-2, is driven by hyperactive cytokine release, or a cytokine storm. The innate sensors that activate production of proinflammatory cytokines and chemokines during COVID-19 remain poorly characterized. In the present study, we show that both TLR2 and MYD88 expression were associated with COVID-19 disease severity. Mechanistically, TLR2 and Myd88 were required for ß-coronavirus-induced inflammatory responses, and TLR2-dependent signaling induced the production of proinflammatory cytokines during coronavirus infection independent of viral entry. TLR2 sensed the SARS-CoV-2 envelope protein as its ligand. In addition, blocking TLR2 signaling in vivo provided protection against the pathogenesis of SARS-CoV-2 infection. Overall, our study provides a critical understanding of the molecular mechanism of ß-coronavirus sensing and inflammatory cytokine production, which opens new avenues for therapeutic strategies to counteract the ongoing COVID-19 pandemic.


Assuntos
COVID-19/imunologia , Proteínas do Envelope de Coronavírus/metabolismo , Síndrome da Liberação de Citocina/imunologia , SARS-CoV-2/imunologia , Receptor 2 Toll-Like/metabolismo , Animais , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/virologia , Chlorocebus aethiops , Síndrome da Liberação de Citocina/diagnóstico , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Leucócitos Mononucleares , Macrófagos , Masculino , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Cultura Primária de Células , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Receptor 2 Toll-Like/antagonistas & inibidores , Receptor 2 Toll-Like/genética , Células Vero
16.
Fish Shellfish Immunol ; 115: 14-21, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34015480

RESUMO

The heavy use of prophylactic antibiotics in aquaculture leads to elevated antibiotic residues, posing a huge hidden danger in aquaculture products and other natural aquatic environments. Therefore, this study aims to isolate probiotics that can replace antibiotics from the gut of grass carp for disease control. Bacillus velezensis B8 was isolated from the gut of grass carp and showed broad-spectrum antimicrobial activity against several fish pathogenic bacteria, including Aeromonas hydrophilis, Aeromonas veronii, Vibrio parahaemolyticus, Escherichia coli, Edwardsiella tarda and Vibrio mimicus. The safety evaluation showed that the strain B8 was non-toxic to grass carp, had no hemolytic activity, and was sensitive to most antibiotics. In vitro study indicated that strain B8 was viable at pH 2-7, had weak tolerance to 0.1% (w/v) bile salt, and could grow at 10°C-40 °C. The grass carps were fed with diets containing 0 (control), 107, and 109 cfu/g of strain B8 for 4 weeks. Various immune parameters were measured at 1, 2, 3, and 4 weeks of post-feeding. The results of non-specific immunoassay showed that diets supplemented with B8 significantly increased alkaline phosphatase (AKP) and superoxide dismutase (SOD) activity in serum samples (p < 0.05). The expression levels of immune-related genes in the kidney and spleen of grass carp were measured. Among them, the expression levels of IgM and TNF-α both in spleen and kidney were significantly increased after 3 and 4 weeks of post-feeding (p < 0.05). The expression of IgD and MHCI in kidney was significantly upregulated in high-dose groups after 2 and 3 weeks of feeding, respectively (p < 0.05). In addition, after 7 days of challenging with A. veronii, the high-dose group and low-dose group had 48% and 53% survival compared to 25% survival for the control group. These results suggest that B. velezensis B8 has the potential to be developed into a microecological preparation for the alternatives of antibiotics in aquaculture.


Assuntos
Bacillus/química , Carpas/imunologia , Resistência à Doença , Doenças dos Peixes/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Imunidade Inata , Probióticos/metabolismo , Aeromonas veronii/fisiologia , Ração Animal/análise , Animais , Dieta/veterinária , Resistência à Doença/efeitos dos fármacos , Relação Dose-Resposta a Droga , Infecções por Bactérias Gram-Negativas/imunologia , Imunidade Inata/efeitos dos fármacos , Probióticos/administração & dosagem , Distribuição Aleatória
17.
BMC Complement Med Ther ; 21(1): 141, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33980308

RESUMO

BACKGROUND: Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections. METHODS: Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea (L.) Moench extract in THP1 monocytes. RESULTS: Gene expression and DNA methylation analysis revealed that Echinaforce® treatment triggers antiviral innate immunity pathways, involving tonic IFN signaling, activation of pattern recognition receptors, chemotaxis and immunometabolism. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi) genomic protective response against viral infections. CONCLUSIONS: Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity through tonic IFN regulation of pattern recognition and chemokine gene expression and DNA repeat hypermethylated silencing of HERVs in monocytes. These results suggest that immunomodulation by Echinaforce® treatment holds promise to reduce symptoms and duration of infection episodes of common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2, with strongly impaired interferon (IFN) response and weak innate antiviral defense.


Assuntos
COVID-19/tratamento farmacológico , Echinacea , Fatores Imunológicos/farmacologia , Monócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , SARS-CoV-2/efeitos dos fármacos , Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Interferons/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/uso terapêutico
18.
Sci Immunol ; 6(59)2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34010142

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, resulting millions of infections and deaths with few effective interventions available. Here, we demonstrate that SARS-CoV-2 evades interferon (IFN) activation in respiratory epithelial cells, resulting in a delayed response in bystander cells. Since pretreatment with IFNs can block viral infection, we reasoned that pharmacological activation of innate immune pathways could control SARS-CoV-2 infection. To identify potent antiviral innate immune agonists, we screened a panel of 75 microbial ligands that activate diverse signaling pathways and identified cyclic dinucleotides (CDNs), canonical STING agonists, as antiviral. Since CDNs have poor bioavailability, we tested the small molecule STING agonist diABZI, and found that it potently inhibits SARS-CoV-2 infection of diverse strains including variants of concern (B.1.351) by transiently stimulating IFN signaling. Importantly, diABZI restricts viral replication in primary human bronchial epithelial cells and in mice in vivo. Our study provides evidence that activation of STING may represent a promising therapeutic strategy to control SARS-CoV-2.


Assuntos
Antivirais/farmacologia , Benzimidazóis/farmacologia , COVID-19/prevenção & controle , Interferons/imunologia , Proteínas de Membrana/agonistas , Animais , Linhagem Celular , Chlorocebus aethiops , Ativação Enzimática/efeitos dos fármacos , Células Epiteliais/virologia , Humanos , Evasão da Resposta Imune/imunologia , Imunidade Inata/efeitos dos fármacos , Imunidade Inata/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/imunologia , Células Vero , Replicação Viral/efeitos dos fármacos
19.
Nat Commun ; 12(1): 2915, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-34006824

RESUMO

Perfluoroalkyl substances (PFAS) are widely used in various manufacturing processes. Accumulation of these chemicals has adverse effects on human health, including inflammation in multiple organs, yet how PFAS are sensed by host cells, and how tissue inflammation eventually incurs, is still unclear. Here, we show that the double-stranded DNA receptor AIM2 is able to recognize perfluorooctane sulfonate (PFOS), a common form of PFAS, to trigger IL-1ß secretion and pyroptosis. Mechanistically, PFOS activates the AIM2 inflammasome in a process involving mitochondrial DNA release through the Ca2+-PKC-NF-κB/JNK-BAX/BAK axis. Accordingly, Aim2-/- mice have reduced PFOS-induced inflammation, as well as tissue damage in the lungs, livers, and kidneys in both their basic condition and in an asthmatic exacerbation model. Our results thus suggest a function of AIM2 in PFOS-mediated tissue inflammation, and identify AIM2 as a major pattern recognition receptor in response to the environmental organic pollutants.


Assuntos
Ácidos Alcanossulfônicos/envenenamento , Proteínas de Ligação a DNA/metabolismo , Fluorcarbonetos/envenenamento , Imunidade Inata/efeitos dos fármacos , Inflamassomos/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Asma/induzido quimicamente , Asma/genética , Asma/metabolismo , Caspase 1/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Proteínas de Ligação a DNA/genética , Poluentes Ambientais/envenenamento , Feminino , Expressão Gênica/efeitos dos fármacos , Imunidade Inata/genética , Imunidade Inata/imunologia , Inflamassomos/genética , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout
20.
Fish Shellfish Immunol ; 114: 311-319, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33845121

RESUMO

An 8-week growth trial was conducted to examine the efficacy of pineapple peel powder (PAPP) on growth rate and immunity of Nile tilapia, O. niloticus. Three hundred Nile tilapia (20.91 ± 0.11 g) were fed five diets containing different levels of PAPP at 0, 10, 20, 30 and 40 g kg-1 PAPP, respectively. After four and eight weeks of the feeding trial, growth rates, and immune responses were tested. A challenge test using Streptococcus agalactiae and relative immune gene expression were performed after eight weeks of PAPP feeding. It was found that skin mucus and serum lysozyme, skin mucus and serum peroxidase, alternative complement, phagocytosis, and respiratory burst activities were significantly increased with the addition of PAPP. The maximum (P ≤ 0.05) innate immune values were noted in fish fed 10 g kg-1 PAPP. Similarly, the up-regulation of IL1, IL8, and LBP gene expressions were also detected in fish fed PAPP diets, with the maximum value was found in 10 g kg-1 PAPP fed fish. The relative percentage of survival (RPS) of Oreochromis niloticus after the challenge test were (56.00%, 72.00%, 60.00%, and 44.00%) for the 5, 10, 20 and 40 g kg-1 PAPP diets, respectively. Fish fed the 10 g kg-1 PAPP supplemented diet achieved the highest (P < 0.05) survival rate against S. agalactiae. Growth and feed efficiency were outstandingly (P < 0.05) enhanced in the PAPP groups. In conclusion, PAPP can be potentially used as a feed additive in Nile tilapia culture under Biofloc system.


Assuntos
Ananas/química , Ração Animal/análise , Ciclídeos , Regulação da Expressão Gênica/imunologia , Imunidade Inata/efeitos dos fármacos , Animais , Dieta/veterinária , Suplementos Nutricionais , Frutas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Infecções Estreptocócicas/imunologia , Infecções Estreptocócicas/prevenção & controle , Infecções Estreptocócicas/veterinária , Streptococcus agalactiae
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