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1.
Int J Mol Sci ; 23(20)2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-36293284

RESUMO

Altitude is the main external environmental pressure affecting the production performance of Tibetan sheep, and the adaptive evolution of many years has formed a certain response mechanism. However, there are few reports on the response of ruminal microbiota and host genomes of Tibetan sheep to high-altitude environments. Here, we conducted an integrated analysis of volatile fatty acids (VFAs), microbial diversity (16S rRNA), epithelial morphology, and epithelial transcriptome in the rumen of Tibetan sheep at different altitudes to understand the changes in ruminal microbiota-host interaction in response to high altitude. The differences in the nutritional quality of forage at different altitudes, especially the differences in fiber content (ADF/NDF), led to changes in rumen VFAs of Tibetan sheep, in which the A/P value (acetic acid/propionic acid) was significantly decreased (p < 0.05). In addition, the concentrations of IgA and IgG in Middle-altitude (MA) and High-altitude Tibetan sheep (HA) were significantly increased (p < 0.05), while the concentrations of IgM were significantly increased in MA (p < 0.05). Morphological results showed that the width of the rumen papilla and the thickness of the basal layer increased significantly in HA Tibetan sheep (p < 0.05). The 16S rRNA analysis found that the rumen microbial diversity of Tibetan sheep gradually decreased with increasing altitude, and there were some differences in phylum- and genus-level microbes at the three altitudes. RDA analysis found that the abundance of the Rikenellaceae RC9 gut group and the Ruminococcaceae NK4A214 group increased with altitudes. Furthermore, a functional analysis of the KEGG microbial database found the "lipid metabolism" function of HA Tibetan sheep to be significantly enriched. WGCNA revealed that five gene modules were enriched in "energy production and conversion", "lipid transport and metabolism", and "defense mechanisms", and cooperated with microbiota to regulate rumen fermentation and epithelial immune barrier function, so as to improve the metabolism and immune level of Tibetan sheep at high altitude.


Assuntos
Microbiota , Rúmen , Ovinos , Animais , Rúmen/química , Propionatos/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Altitude , Interações entre Hospedeiro e Microrganismos , Tibet , Ácidos Graxos Voláteis/metabolismo , Acetatos/metabolismo , Imunoglobulina A/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo
2.
Int J Mol Sci ; 23(19)2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36233099

RESUMO

Toll-like receptor 9 (TLR9) is activated by unmethylated cytosine-phosphate-guanosine (CpG) dinucleotides found in the genomes of pathogens such as Epstein-Barr virus (EBV). The aim of this study was to determine the role of TLR9 in the immunopathogenesis of IgA nephropathy (IgAN) and membranoproliferative glomerulonephritis (MPGN) in the context of Epstein-Barr virus (EBV) infection. For this purpose, the frequency of TLR9-positive monocytes and dendritic cells (DCs, i.e., BDCA-1; myeloid dendritic cells, and BDCA-2; plasmocytoid dendritic cells) was studied, and a quantitative analysis of the concentration of TLR9 in the serum of patients diagnosed with IgAN and MPGN was undertaken. Higher frequencies of TLR9-positive DCs and monocytes in IgAN and MPGN patients were observed as compared with the control group. Patients diagnosed with GN exhibited a higher percentage of BDCA-1+CD19- and BDCA-2+CD123+ DCs than patients in the control group. Moreover, serum TLR9 concentration was shown to be significantly correlated with EBV DNA copy number/µg DNA, IgG, IgM, serum albumin, total protein in 24-h urine collection test and the frequency of BDCA-2+CD123+ DCs in peripheral blood. Our findings confirm that TLR9 may be involved in the development of IgAN and MPGN.


Assuntos
Infecções por Vírus Epstein-Barr , Glomerulonefrite por IGA , Glomerulonefrite Membranoproliferativa , Receptor Toll-Like 9 , Citosina/metabolismo , Células Dendríticas/metabolismo , Infecções por Vírus Epstein-Barr/patologia , Glomerulonefrite por IGA/patologia , Glomerulonefrite Membranoproliferativa/metabolismo , Guanosina/metabolismo , Herpesvirus Humano 4 , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Subunidade alfa de Receptor de Interleucina-3/metabolismo , Monócitos/metabolismo , Fosfatos/metabolismo , Albumina Sérica/metabolismo , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/metabolismo
3.
Front Immunol ; 13: 968815, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189218

RESUMO

Currently immunomodulatory compounds are under investigation for use in patients with cardiovascular disease, caused by atherosclerosis. These trials, using recurrent cardiovascular events as endpoint, require enrollment of large patient groups. We investigated the effect of key risk factors for atherosclerosis development, ageing and smoking, on the immune system, with the objective to identify biomarkers differentiating between human populations, and potentially serving as endpoints for future phase 1B trials with immunomodulatory compounds. Blood was collected from young healthy volunteers (aged 18-25 years, n=30), young smokers (18-25 years, n=20), elderly healthy volunteers (>60 years, n=20), heavy smokers (>45 years, 15 packyears, n=11) and patients with stable coronary artery disease (CAD) (>60 years, n=27). Circulating immune cell subsets were characterized by flow cytometry, and collected plasma was evaluated by proteomics (Olink). Clear ageing effects were observed, mostly illustrated by a lower level in CD8+ and naïve CD4+ and CD8+ T cells, with an increase in CD4+ and CD8+ effector memory T cells in elderly healthy volunteers compared to young healthy volunteers. Heavy smokers showed a more inflammatory cellular phenotype, especially a shift in Th1/Th2 ratio: higher Th1 and lower Th2 percentages compared to young healthy volunteers. A significant decrease in circulating atheroprotective oxLDL-specific IgM was found in patients with CAD compared to young healthy volunteers. Elevated pro-inflammatory and chemotactic proteins TREM1 and CCL11 were observed in elderly volunteers compared to young volunteers. In addition, heavy smokers had an increase in pro-inflammatory cytokine IL-6 and lysosomal protein LAMP3. These data show that ageing and smoking are associated with an inflammatory immunophenotype, and that heavy smokers or aged individuals may serve as potential populations for future clinical trials investigating immunomodulatory drugs targeted for cardiovascular disease.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Adolescente , Adulto , Envelhecimento , Aterosclerose/metabolismo , Biomarcadores/metabolismo , Linfócitos T CD8-Positivos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Citocinas/metabolismo , Humanos , Imunoglobulina M/metabolismo , Interleucina-6/metabolismo , Pessoa de Meia-Idade , Fumar/efeitos adversos , Células Th1 , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Adulto Jovem
4.
Fish Shellfish Immunol ; 130: 479-489, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36162774

RESUMO

Sablefish (Anoplopoma fimbria) are an emerging aquaculture species native to the continental shelf of the northern Pacific Ocean. There is limited information on both innate and adaptive immunity for this species and new tools are needed to determine antibody response following vaccination or disease outbreaks. In this paper, a monoclonal antibody, UI-25A, specific to sablefish IgM was produced in mice. Western blotting confirmed UI-25A recognizes the heavy chain of IgM and does not cross react to proteins or carbohydrates in serum of four other teleost species. An ELISA was developed to measure Aeromonas salmonicida specific IgM in the plasma of sablefish from a previous experiment where fish were immunized with a proprietary A. salmonicida vaccine. UI-25A was used in Western blot analyses to identify immunogenic regions of A. salmonicida recognized by this specific IgM from vaccinated sablefish. Immunofluorescent staining also demonstrated the ability of UI-25A to recognize membrane-bound IgM and identify IgM + cells in the head kidney. These results demonstrate the usefulness of UI-25A as a tool to improve the understanding of antibody-mediated immunity in sablefish as well as to provide valuable information for vaccine development and expansion of aquaculture efforts for this fish species.


Assuntos
Anticorpos Monoclonais , Perciformes , Animais , Anticorpos Monoclonais/metabolismo , Western Blotting , Carboidratos , Ensaio de Imunoadsorção Enzimática/veterinária , Peixes/metabolismo , Imunoglobulina M/metabolismo , Camundongos , Coloração e Rotulagem
5.
Ecotoxicol Environ Saf ; 244: 114050, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36063614

RESUMO

Exposure to ammonia can cause convulsions, coma, and death. In this study, we investigate the effects of ammonia exposure on immunoregulatory and neuroendocrine changes in Takifugu rubripes. Fish were sampled at 0, 12, 24, 48, and 96 h following exposure to different ammonia concentrations (0, 5, 50, 100, and 150 mg/L). Our results showed that exposure to ammonia significantly reduced the concentrations of C3, C4, IgM, and LZM whereas the heat shock protein 70 and 90 levels significantly increased. In addition, the transcription levels of Mn-SOD, CAT, GRx, and GR in the liver were significantly upregulated following exposure to low ammonia concertation, however, downregulated with increased exposure time. These findings suggest that ammonia poisoning causes oxidative damage and suppresses plasma immunity. Ammonia exposure also resulted in the elevation and depletion of the T3 and T4 levels, respectively. Furthermore, ammonia stress induced an increase in the corticotrophin-releasing hormone, adrenocorticotropic hormone, and cortisol levels, and a decrease in dopamine, noradrenaline, and 5-hydroxytryptamine levels in the brain, illustrating that ammonia poisoning can disrupt the endocrine and neurotransmitter systems. Our results provide insights into the mechanisms underlying the neurotoxic effects of ammonia exposure, which helps to assess the ecological and environmental health risks of this contaminant in marine fish.


Assuntos
Amônia , Takifugu , Hormônio Adrenocorticotrópico/metabolismo , Amônia/metabolismo , Animais , Encéfalo/metabolismo , Dopamina/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Hidrocortisona/metabolismo , Imunidade , Imunoglobulina M/metabolismo , Neurotransmissores/metabolismo , Norepinefrina/metabolismo , Serotonina/metabolismo , Superóxido Dismutase/metabolismo , Takifugu/metabolismo , Glândula Tireoide/metabolismo , Hormônios Tireóideos/metabolismo
6.
Eur J Cancer ; 175: 86-98, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36096041

RESUMO

INTRODUCTION: Glioma is the most common and most invasive primary central nervous system tumour, and it is urgent to develop new specific therapeutic targets. Studies have confirmed that epithelial-derived tumour cells promote tumour cell proliferation and metastasis by secreting a large number of immunoglobulins (Igs), but the role of tumour-derived Igs in glioma has never been reported. METHODS: The Gene Expression Profiling Interactive Analysis and Chinese Glioma Genome Atlas databases were used to analyse the Ig transcription and its correlation with the prognosis of patients with glioma. Immunohistochemistry and immunofluorescence were used to detect the protein expression of IgG and IgM in the glioma tissues of patients and glioma cell lines. When IgG was knocked down by small interfering RNA or knocked out by CRISPR-Cas9, the function of proliferation and migration of glioma cells were analysed by CCK-8, clone formation, wound healing, and transwell assays. Changes in proteins and their phosphorylation in signalling pathways were detected by western blotting. The nude mouse subcutaneous tumour-bearing model was established to analyse the effect of IgG in vivo. RESULTS: The transcriptional level of IgG was pretty high in glioma tissues and was positively correlated with high WHO grade, recurrence, and poor prognosis. The expression of IgG and IgM was found in tumour tissues and human glioma cell lines U87 and U251, and the main expression form was secreted. Decreased IgG inhibited the proliferation and migration of glioma cells. Knockout or knockdown of IgG downregulated the phosphorylation of the key molecules in the MAPK and PI3K/Akt pathway through the HGF/SF-Met or FAK/Src pathway. In vivo tumourigenesis mouse model confirmed that reduced IgG expression inhibited glioma growth. CONCLUSION: Ig was expressed in glioma tissues and cell lines, and a high expression level predicted a poor prognosis of patients. Glioma-derived IgG promoted glioma cell proliferation and migration through the HGF/SF-Met or FAK/Src pathway.


Assuntos
Neoplasias Encefálicas , Glioma , Animais , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma/patologia , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Imunoglobulina G/genética , Imunoglobulina G/metabolismo , Imunoglobulina M/genética , Imunoglobulina M/metabolismo , Camundongos , Camundongos Knockout , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/metabolismo
7.
Sci Total Environ ; 850: 157997, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35964742

RESUMO

The purpose of this study was to investigate the effects of dietary aflatoxin B1 (AFB1) on growth performance and AFB1 biotransformation, and hepatic oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and inflammation in northern snakehead (Channa argus). A total of 600 northern snakeheads (7.52 ± 0.02 g) were divided into five groups (three replicates/group) and fed the diets with AFB1 at concentrations of 0, 50, 100, 200, and 400 ppb for 8 weeks. The results demonstrated that dietary AFB1 (≥ 200 ppb) reduced FBW, WG, and SGR. 100, 200, and 400 ppb AFB1 treatment groups significantly decreased the PER, CRP, C3, C4, IgM, and LYS levels in northern snakehead, while FCR was significant increased. Moreover, dietary AFB1 (100, 200, and 400 ppb) increased cyp1a, cyp1b (except 400 ppb), and cyp3a mRNA expression levels, while reducing the GST enzymatic activity and mRNA expression levels in northern snakehead. Furthermore, AFB1 (≥ 100 ppb) increased ROS, MDA, and 8-OHdG levels, and grp78, ire1, perk, jnk, chop, and traf2 mRNA expression levels, and decreased SOD, CAT, GSH-Px, and GSH (except 100 ppb) levels and the gene expression levels of cat, gsh-px (except 100 ppb), and Cu/Zn sod. In addition, AFB1 (100, 200, and 400 ppb) up-regulated the cyt-c, bax, cas-3, and cas-9 mRNA levels in the liver, while down-regulating the bcl-2 expression levels. Meanwhile, the expression levels of nf-κb, tnf-α (except 100 ppb), il-1ß, and il-8 in the liver were up-regulated in AFB1 treatment groups (≥ 100 ppb), while the iκbα mRNA levels were down-regulated. In summary, dietary AFB1 reduced growth performance and humoral immunity in northern snakehead. Meanwhile, the cyclic occurrence of oxidative stress and ER stress, and induced apoptosis and inflammation, is one of the main reasons for AFB1-induced liver injury in the northern snakehead, which will provide valuable information and a fresh perspective for further research into AFB1-induced liver injury in fish.


Assuntos
Aflatoxina B1 , Doença Hepática Crônica Induzida por Substâncias e Drogas , Aflatoxina B1/toxicidade , Animais , Apoptose , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Citocromo P-450 CYP3A/metabolismo , Dieta/veterinária , Estresse do Retículo Endoplasmático , Peixes/metabolismo , Imunoglobulina M/metabolismo , Imunoglobulina M/farmacologia , Inflamação/induzido quimicamente , Interleucina-8/metabolismo , Fígado/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B , Estresse Oxidativo , Proteínas Serina-Treonina Quinases , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fator 2 Associado a Receptor de TNF/metabolismo , Fator 2 Associado a Receptor de TNF/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína X Associada a bcl-2/farmacologia
8.
Fish Physiol Biochem ; 48(5): 1183-1192, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35945370

RESUMO

This study aimed to investigate the effects of transport stress on the physiological responses and immunity of Megalobrama amblycephala (blunt snout bream). Fish (109.67 ± 1.51 g) were sampled at nine time points: before transport (control), at 0 h, 1 h, 3 h, 6 h, 12 h, 24 h, 3 days, and 7 days after 4 h of medium-distance transportation, and four fish were sampled in each time point. The results showed that plasma cortisol, triiodothyronine (T3), complement component 3 (C3), complement component 4 (C4), immunoglobulin M (IgM) and nitrogen monoxide (NO) concentrations, and alternative complement pathway (ACH50), acid phosphatase (ACP), and myeloperoxidase (MPO) activities all reached the peak at 0 h after transportation; C4 and NO concentrations as well as ACP and MPO activities returned to the control level after 1 h, ACH50 activity as well as cortisol, T3, and IgM concentration returned to the control level after 12 h, and C3 concentration returned to the control level after 24 h respectively. Plasma glucose and total protein concentrations as well as lysozyme activity all reached the peak at 1 h after transportation, total protein concentration and lysozyme activity returned to the control level after 3 h, and glucose concentration returned to the control level after 6 h (P < 0.05). Liver heat shock protein 70 expression reached the peak at 1 h after transportation, and returned to the control level after 24 h; liver heat shock protein 90 expression reached the peak at 0 h after transportation and returned to the control level after 12 h (P < 0.05). Overall, these findings suggested that 4 h of medium-distance transportation caused stress response of blunt snout bream, and transport stress had a significant effect on plasma indicators. But the recovery of 24 h after transport could return the physiological response, immune indexes, and the expression of heat shock protein to the normal level. This also provided data support for the medium-distance transportation of blunt snout bream in the future.


Assuntos
Cyprinidae , Cipriniformes , Animais , Ração Animal/análise , Cyprinidae/fisiologia , Peroxidase/metabolismo , Complemento C3/metabolismo , Hidrocortisona/metabolismo , Muramidase , Óxido Nítrico/metabolismo , Glicemia , Tri-Iodotironina/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/metabolismo , Fosfatase Ácida/metabolismo , Imunoglobulina M/metabolismo , Complemento C4
9.
Fish Shellfish Immunol ; 128: 574-581, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36007828

RESUMO

Nanotechnology has recently played a key role in tackling many aquacultures issues. Hence, the present study targets the evaluation of dietary inclusion of nano iron oxide (nFe2O3) on growth performance, hematology, immune-antioxidant responses, ionic regulation and expression of related genes in Nile tilapia (Oreochromis niloticus). Fish were fed supplementary nFe2O3 at rates of zero (control), 0.5, and 1 g/kg diet for 30 days. Obtained data demonstrated that nFe2O3 significantly (P < 0.05) augmented growth performance (final weight and length, body mass gain, specific growth rate, feed conversion ratio, and length gain rate). Hematological picture {RBCs, Hb, MCV, MCH and MCHC, and leukocytes interpretations (WBCs and monocytes)}; and biochemical indexes including (AST and ALT; total protein; and glucose, and cortisol) were significantly (P < 0.05) improved in nFe2O3 supplemented groups. Plasma ionic concentration was also altered with nFe2O3 supplementation, and 1g nFe2O3 revealed the most marked increase in plasma (Na+) potassium (K+) levels. Similarly, IgM, nitrous oxide (NO), and lysozyme activity, plus superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities showed a remarkable improvement in 1g nFe2O3 group compared to the control. Expression of Insulin-Like Growth Factor-1 (IGF-1) and interleukin 1-ß (IL-1ß) genes were significantly up-regulated in nFe2O3 supplemented groups. Briefly, dietary nFe2O3 inclusion had enhanced properties on growth; hemato-biochemical; immune, antioxidative profiles; and related genes expression of O. niloticus, with a recommended concentration of 1g nFe2O3.


Assuntos
Ciclídeos , Doenças dos Peixes , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Dieta/veterinária , Suplementos Nutricionais , Expressão Gênica , Glucose/metabolismo , Glutationa Peroxidase/metabolismo , Hidrocortisona/metabolismo , Imunoglobulina M/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Interleucina-1/metabolismo , Muramidase/metabolismo , Óxido Nitroso/metabolismo , Potássio/metabolismo , Superóxido Dismutase/metabolismo
10.
Hypertension ; 79(10): 2239-2249, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35950503

RESUMO

BACKGROUND: The spontaneously hypertensive rat (SHR) is extensively used to study hypertension. Gut microbiota dysbiosis is a notable feature in SHR for reasons unknown. Immunoglobulin A (IgA) is a major host factor required for gut microbiota homeostasis. We hypothesized that inadequate IgA contributes to gut microbiota dysbiosis in SHR. METHODS: IgA was measured in feces, cecum, serum, liver, gut-associated lymphoid tissue, and milk from SHR and Wistar Kyoto rats. IgA regulatory factors like IgM, IgG, and pIgR (polymeric immunoglobulin receptor) were analyzed. IgA and IgG antibodies and blood pressure (BP) were measured before and after administrating a bacterial antigen (ie, flagellin). RESULTS: Compared with Wistar Kyoto rats, SHR displayed remarkably near-deficient IgA levels accompanied by compensatory increases in serum IgM and IgG and gut-liver pIgR expression. Inadequate milk IgA in SHR emphasized this immune defect stemmed from the neonatal stage. Reduced IgA+ B cells in circulation and Peyer patches indicated a possible reason for the lower IgA in SHR. Noteworthy, a genetic insufficiency was unlikely because administering flagellin to SHR induced anti-flagellin IgA antibodies. This immune response surprisingly accelerated hypertension development in SHR, suggesting IgA quiescence may help maintain lower BP. CONCLUSIONS: This study is the first to reveal IgA deficiency in SHR as one host factor associated with gut microbiota dysbiosis and invigorates future research to determine the pathophysiological role of IgA in hypertension.


Assuntos
Hipertensão , Deficiência de IgA , Animais , Pressão Sanguínea , Disbiose , Imunoglobulina A/metabolismo , Imunoglobulina G , Imunoglobulina M/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
11.
Fish Shellfish Immunol ; 128: 348-359, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35963561

RESUMO

The experiment aimed to investigate the alteration of tea polyphenols (TP) in growth and immunity for hybrid grouper (Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂) fed high-lipid diets. Six concentrations of TP (0, 0.01, 0.02, 0.04, 0.08, 0.16%, named TP1 (basic diet control), TP2, TP3, TP4, TP5, TP6) were supplied in isonitrogenous (51%) and isolipidic (16.7%) experimental diets. These diets were fed to the juvenile grouper (8.68 ± 0.22 g) for 8 weeks. The results showed that dietary TP significantly increased the weight gain rate and specific growth rate (P < 0.05), compared with the control group. The protein efficiency ratio in TP4 group was significantly higher than that of the control group (P < 0.05). TP supplement in high-lipid diets increased antioxidant capacity in the serum (CAT, GSH-Px, T-AOC) and liver (SOD, CAT, GSH-Px, T-AOC). Additionally, dietary TP decreased oxidative stress (ROS, MDA) and improved immunity (ACP, AKP, LYS, IgM) in the liver. The histology of hepatic tissue indicated that dietary TP alleviated pathological symptoms caused by high-lipid diets. Compared with the control group, appropriate dietary TP significantly up-regulated expression of sod, cat, gsh-px, nrf2, keap1, hsp70, hsp90, myd88, tnfα and down-regulated expression of tlr22, il8, il1ß, il10 in the liver (P < 0.05). In the head kidney, expression of myd88, il1ß, tnfα and il6 were significantly up-regulated and expression of tlr22 and il10 were significantly down-regulated by dietary TP (P < 0.05). After the challenge of Vibrio harveyi, survival rate in higher doses of TP group (TP4 âˆ¼ TP6) was evidently higher, compared with the control group. In conclusion, TP supplement in high-lipid diets improved antioxidant capacity and enhanced immunity of grouper. We speculate that TP may play the role of an immunostimulant, enhancing immunity and disease resistance by cytokine-medicated immune responses. Based on the second-order regression, 0.092-0.106% tea polyphenols were recommended in juvenile grouper high-lipid diets.


Assuntos
Bass , Adjuvantes Imunológicos , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Dieta/veterinária , Suplementos Nutricionais/análise , Imunidade Inata , Imunoglobulina M/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Interleucina-8 , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lipídeos , Fator 88 de Diferenciação Mieloide/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Polifenóis , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Chá , Fator de Necrose Tumoral alfa/metabolismo
12.
Brain Behav Immun ; 106: 11-20, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35914698

RESUMO

Schizophrenia (SZ) is influenced by genetic and environmental factors, and associated with chronic neuroinflammation. If the symptoms express after adolescence, environmental impacts are more substantial, and the disease is defined as adult-onset schizophrenia (AOS). Effects of environmental factors on antibody responses such as Escherichia coli (E. coli) to immunoglobulin G (IgG) and immunoglobulin M (IgM) might increase the severity of symptoms in SZ via the gut-brain axis. The purpose of this study is to reveal antibody profiles of SZ against bacterial protein antigens. We analyzed the IgG and IgM antibodies using E. coli proteome microarrays from 80 SZ patients and 40 healthy controls (HC). Using support vector machine to select panels of proteins differentiating between groups and conducted enrichment analysis for those proteins. We identified that the groL, pldA, yjjU, livG, and ftsE can classify IgGs in AOS vs HC achieved accuracy of 0.7. The protein yjjU, livG and ftsE can form the best combination panel to classify IgG in AOS vs HC with accuracy of 0.8. The enrichment results are highly related to ABC (ATP binding cassette) transporter in the protein domain and cellular component. We further found that the human ATP binding cassette subfamily b member 1 (ABCB1) autoantibody level in AOS is significantly higher than in HC. The findings suggest that AOS had different immunoglobulin production compared to early-onset schizophrenia (EOS) and HC. We also identified potential antibody biomarkers of AOS and found their antigens are enriched in ABC transporter related domains, including human ABCB1 protein.


Assuntos
Proteínas de Escherichia coli , Esquizofrenia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Trifosfato de Adenosina , Adolescente , Adulto , Proteínas de Bactérias/metabolismo , Escherichia coli , Proteínas de Escherichia coli/metabolismo , Humanos , Imunoglobulina G , Imunoglobulina M/metabolismo , Proteoma/metabolismo
13.
Int J Mol Sci ; 23(16)2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36012490

RESUMO

Previous studies imply that peripheral blood leukocytes (PBLs) may play an important role in systemic lymphocystis disease virus (LCDV) dissemination, but whether the PBLs are susceptible and permissive to LCDV infection and the dissemination mechanism need to be clarified. In this study, LCDV was firstly confirmed to infect the PBLs in flounder (Paralichthys olivaceus) in vivo, and to replicate in PBLs in vitro. Subsequently, the 27.8 kDa receptor protein (27.8R), a functional receptor mediating LCDV infection in flounder gill cells, was shown to locate on the cell membrane of PBLs and co-localize with LCDV in PBLs, while blocking of the 27.8R via pre-incubation of anti-27.8R MAb with the PBLs could obviously inhibit LCDV infection, revealing the 27.8R as a receptor for LCDV entry into PBLs. Multicolor fluorescence imaging studies verified that IgM+ and IgD+ B-lymphocyte were involved in LCDV infection. In the sorted IgM+ B-cells, 27.8R+ and LCDV+ signals were simultaneously observed, and LCDV copy numbers increased with time, indicating that IgM+ B-cells expressed the 27.8R and were permissive to LCDV infection. Furthermore, the dynamic changes of IgM+, 27.8R+, LCDV+ and LCDV+/IgM+ PBLs were monitored during the early phase of LCDV infection. It was found that the percentage of IgM+ B-cells in PBLs clearly declined first and then increased, suggesting LCDV infection facilitated damage to B-cells, whereas the amounts of 27.8R+ and LCDV+ PBLs, as well as LCDV-infected IgM+ B-cells, showed an opposite trend. These results proved that IgM+ B-lymphocytes could be infected by LCDV via a receptor-mediated mechanism and support viral replication, which provided novel insights for the first time into the role of B-lymphocytes in LCDV dissemination and pathogenesis in teleost fish.


Assuntos
Infecções por Vírus de DNA , Doenças dos Peixes , Linguado , Iridoviridae , Animais , Linfócitos B/metabolismo , Infecções por Vírus de DNA/metabolismo , Imunoglobulina M/metabolismo
14.
Artigo em Inglês | MEDLINE | ID: mdl-36030005

RESUMO

Pyraclostrobin (PYR), a strobilurin fungicide, has been widely used to control fungal diseases, posing potential risk to aquatic organisms. However, the toxic effects of PYR to fish remained largely unknown. In this study, common carp (Cyprinus carpio L.) was exposed to environmentally relevant levels of PYR (0, 0.5 and 5.0 µg/L) for 30 days to assess its chronic toxicity and potential toxicity mechanism. The results showed that long-term exposure to PYR induced hepatopancreas damage as evident by increased in serum transaminase activities (AST and ALT). Moreover, PYR exposure remarkably enhanced the expressions of hsp70 and hsp90, decreased the levels of antioxidant enzymes and biomarkers and promoted the reactive oxygen species (H2O2 and O2-) and MDA contents in carp hepatopancreas. PYR exposure also upregulated apoptosis-related genes (bax, apaf-1, caspase-3 and caspase-9) and reduced anti-apoptosis gene bcl-2 in fish hepatopancreas. Moreover, PYR exposure altered the expressions of inflammatory cytokines (IL-1ß, IL-6, TNF-α and TGF-ß) in the serum and hepatopancreas and the level of NF-κB p65 in the hepatopancreas. Further research indicated that PYR exposure markedly changed the levels of immune parameters (LYZ, C3, IgM, ACP and AKP) in the serum and/or hepatopancreas, indicating that chronic PYR exposure also has immunotoxicity on fish. Additionally, we found that PYR exposure upregulated p38 and jnk MAPK transcription levels, suggesting that MAPK may be play important role in PYR-induced apoptosis and inflammatory response in the hepatopancreas of common carp. In summary, PYR exposure induced oxidative stress, triggered apoptosis, inflammatory and immune response in common carp, which can help to elucidate the possible toxicity mechanism of PYR in fish.


Assuntos
Carpas , Fungicidas Industriais , Animais , Antioxidantes/metabolismo , Carpas/metabolismo , Caspase 3/metabolismo , Caspase 9/metabolismo , Fungicidas Industriais/toxicidade , Hepatopâncreas/metabolismo , Peróxido de Hidrogênio/metabolismo , Imunoglobulina M/metabolismo , Imunoglobulina M/farmacologia , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Estrobilurinas/metabolismo , Estrobilurinas/toxicidade , Transaminases , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo
15.
Eur J Immunol ; 52(10): 1630-1639, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35862268

RESUMO

In past years ex vivo and in vivo experimental approaches involving human naive B cells have proven fundamental for elucidation of mechanisms promoting B cell differentiation in both health and disease. For such studies, it is paramount that isolation strategies yield a population of bona fide naive B cells, i.e., B cells that are phenotypically and functionally naive, clonally non-expanded, and have non-mutated BCR variable regions. In this study different combinations of common as well as recently identified B cell markers were compared to isolate naive B cells from human peripheral blood. High-throughput BCR sequencing was performed to analyze levels of somatic hypermutation and clonal expansion. Additionally, contamination from mature mutated B cells intrinsic to each cell-sorting strategy was evaluated and how this impacts the purity of obtained populations. Our results show that current naive B cell isolation strategies harbor contamination from non-naive B cells, and use of CD27-IgD+ is adequate but can be improved by including markers for CD45RB glycosylation and IgM. The finetuning of naive B cell classification provided herein will harmonize research lines using naive B cells, and will improve B cell profiling during health and disease, e.g. during diagnosis, treatment, and vaccination strategies.


Assuntos
Subpopulações de Linfócitos B , Subpopulações de Linfócitos B/metabolismo , Separação Celular , Glicosilação , Humanos , Imunoglobulina D/metabolismo , Isotipos de Imunoglobulinas/metabolismo , Imunoglobulina M/metabolismo , Memória Imunológica/genética , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
16.
Transpl Immunol ; 74: 101661, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35787933

RESUMO

INTRODUCTION: Pig heart xenotransplantation might act as a bridge in infants with complex congenital heart disease (CHD) until a deceased human donor heart becomes available. Infants develop antibodies to wild-type (WT, i.e., genetically-unmodified) pig cells, but rarely to cells in which expression of the 3 known carbohydrate xenoantigens has been deleted by genetic engineering (triple-knockout [TKO] pigs). Our objective was to test sera from children who had undergone palliative surgery for complex CHD (and who potentially might need a pig heart transplant) to determine whether they had serum cytotoxic antibodies against TKO pig cells. METHODS: Sera were obtained from children with CHD undergoing Glenn or Fontan operation (n = 14) and healthy adults (n = 8, as controls). All of the children had complex CHD and had undergone some form of cardiac surgery. Seven had received human blood transfusions and 3 bovine pericardial patch grafts. IgM and IgG binding to WT and TKO pig red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs) were measured by flow cytometry, and killing of PBMCs by a complement-dependent cytotoxicity assay. RESULTS: Almost all children and adults demonstrated relatively high IgM/IgG binding to WT RBCs, but minimal binding to TKO RBCs (p < 0.0001 vs WT), although IgG binding was greater in children than adults (p < 0.01). All sera showed IgM/IgG binding to WT PBMCs, but this was much lower to TKO PBMCs (p < 0.0001 vs WT) and was greater in children than in adults (p < 0.05). Binding to both WT and TKO PBMCs was greater than to RBCs. Mean serum cytotoxicity to WT PBMCs was 90% in both children and adults, whereas to TKO PBMCs it was only 20% and < 5%, respectively. The sera from 6/14 (43%) children were cytotoxic to TKO PBMCs, but no adult sera were cytotoxic. CONCLUSIONS: Although no children had high levels of antibodies to TKO RBCs, 13/14 demonstrated antibodies to TKO PBMCs, in 6 of these showed mild cytotoxicity. As no adults had cytotoxic antibodies to TKO PBMCs, the higher incidence in children may possibly be associated with their exposure to previous cardiac surgery and biological products. However, the numbers were too small to determine the influence of such past exposures. Before considering pig heart xenotransplantation for children with CHD, testing for antibody binding may be warranted.


Assuntos
Cardiopatias Congênitas , Transplante de Coração , Animais , Animais Geneticamente Modificados , Bovinos , Cardiopatias Congênitas/cirurgia , Humanos , Imunoglobulina G/metabolismo , Imunoglobulina M/metabolismo , Lactente , Leucócitos Mononucleares , Cuidados Paliativos , Suínos , Doadores de Tecidos , Transplante Heterólogo
17.
Front Immunol ; 13: 809264, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720313

RESUMO

Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum (Pf) merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against Pf develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, full-length Pf merozoite surface protein 1 (PfMSP1FL), in individuals from a region in Uganda with high Pf transmission. Our results showed that PfMSP1FL-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ PfMSP1FL-specific classical MBCs. In contrast, anti-PfMSP1FL plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against PfMSP1FL, with broadening of the response against non-3D7 strains in adults. The B cell receptors encoded by PfMSP1FL-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable PfMSP1 protein. Proteomics analysis of PfMSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to B cell receptors of PfMSP1FL-specific MBCs, anti-PfMSP119 IgGs had high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the PfMSP1-specific humoral immune response with cumulative Pf exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of PfMSP1 variants by the plasma IgG repertoire.


Assuntos
Malária , Proteína 1 de Superfície de Merozoito , Adulto , Animais , Anticorpos Antiprotozoários , Formação de Anticorpos , Criança , Humanos , Imunoglobulina G , Imunoglobulina M/metabolismo , Células B de Memória , Merozoítos , Plasmodium falciparum , Receptores de Antígenos de Linfócitos B/metabolismo , Uganda
18.
J Exp Med ; 219(7)2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35670812

RESUMO

Regulatory T (Treg) cells represent a specialized lineage of suppressive CD4+ T cells whose functionality is critically dependent on their ability to migrate to and dwell in the proximity of cells they control. Here we show that continuous expression of the chemokine receptor CXCR4 in Treg cells is required for their ability to accumulate in the bone marrow (BM). Induced CXCR4 ablation in Treg cells led to their rapid depletion and consequent increase in mature B cells, foremost the B-1 subset, observed exclusively in the BM without detectable changes in plasma cells or hematopoietic stem cells or any signs of systemic or local immune activation elsewhere. Dysregulation of BM B-1 B cells was associated with a highly specific increase in IgM autoantibodies and total serum IgM levels. Thus, Treg cells control autoreactive B-1 B cells in a CXCR4-dependent manner. These findings have significant implications for understanding the regulation of B cell autoreactivity and malignancies.


Assuntos
Subpopulações de Linfócitos B , Linfócitos T Reguladores , Subpopulações de Linfócitos B/metabolismo , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Imunoglobulina M/metabolismo , Receptores CXCR4/metabolismo
19.
Front Immunol ; 13: 891316, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572548

RESUMO

Glycosylation of CD45RB (RB+) has recently been identified to mark antigen-experienced B cells, independent of their CD27 expression. By using a novel combination of markers including CD45RB glycosylation, CD27 and IgM/IgD isotype expression we segregated human peripheral blood B cell subsets and investigated their IGHV repertoire and in vitro functionality. We observed distinct maturation stages for CD27-RB+ cells, defined by differential expression of non-switched Ig isotypes. CD27-RB+ cells, which only express IgM, were more matured in terms of Ig gene mutation levels and function as compared to CD27-RB+ cells that express both IgM and IgD or cells that were CD27-RB-. Moreover, CD27-RB+IgM+ cells already showed remarkable rigidity in IgM isotype commitment, different from CD27-RB+IgMD+ and CD27-RB- cells that still demonstrated great plasticity in B cell fate decision. Thus, glycosylation of CD45RB is indicative for antigen-primed B cells, which are, dependent on the Ig isotype, functionally distinct.


Assuntos
Subpopulações de Linfócitos B , Antígenos Comuns de Leucócito/imunologia , Subpopulações de Linfócitos B/metabolismo , Glicosilação , Humanos , Imunoglobulina D/metabolismo , Isotipos de Imunoglobulinas/metabolismo , Imunoglobulina M/metabolismo , Membro 7 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo
20.
Int J Mol Sci ; 23(10)2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35628381

RESUMO

The MYD88 gene has a physiological role in the innate immune system. Somatic mutations in MYD88, including the most common L265P, have been associated with the development of certain types of lymphoma. MYD88L265P is present in more than 90% of patients with Waldenström's macroglobulinemia (WM) and IgM monoclonal gammopathy of undetermined significance (IgM-MGUS). The absence of MYD88 mutations in WM patients has been associated with a higher risk of transformation into aggressive lymphoma, resistance to certain therapies (BTK inhibitors), and shorter overall survival. The MyD88 signaling pathway has also been used as a target for specific therapies. In this review, we summarize the clinical applications of MYD88 testing in the diagnosis, prognosis, follow-up, and treatment of patients. Although MYD88L265P is not specific to WM, few tumors present a single causative mutation in a recurrent position. The role of the oncogene in the pathogenesis of WM is still unclear, especially considering that the mutation can be found in normal B cells of patients, as recently reported. This may have important implications for early lymphoma detection in healthy elderly individuals and for the treatment response assessment based on a MYD88L265P analysis.


Assuntos
Mutação , Fator 88 de Diferenciação Mieloide , Macroglobulinemia de Waldenstrom , Idoso , Humanos , Imunoglobulina M/genética , Imunoglobulina M/metabolismo , Linfoma/genética , Linfoma/metabolismo , Linfoma de Células B/genética , Linfoma de Células B/metabolismo , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismo , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/genética , Macroglobulinemia de Waldenstrom/metabolismo
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