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1.
PLoS Negl Trop Dis ; 13(8): e0007650, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31412039

RESUMO

Enteric fevers, caused by the Salmonella enterica serovars Typhi (ST), Paratyphi A (PA) and Paratyphi B (PB), are life-threatening illnesses exhibiting very similar clinical symptoms but with distinct epidemiologies, geographical distributions and susceptibilities to antimicrobial treatment. Nevertheless, the mechanisms by which the host recognizes pathogens with high levels of homology, such as these bacterial serovars, remain poorly understood. Using a three-dimensional organotypic model of the human intestinal mucosa and PA, PB, and ST, we observed significant differences in the secretion patterns of pro-inflammatory cytokines and chemokines elicited by these serovars. These cytokines/chemokines were likely to be co-regulated and influenced the function of epithelial cells, such as the production of IL-8. We also found differing levels of polymorphonuclear leukocyte (PMN) migration among various infection conditions that either included or excluded lymphocytes and macrophages (Mϕ), strongly suggesting feedback mechanisms among these cells. Blocking experiments showed that IL-1ß, IL-6, IL-8, TNF-α and CCL3 cytokines were involved in the differential regulation of migration patterns. We conclude that the crosstalk among the lymphocytes, Mϕ, PMN and epithelial cells is cytokine/chemokine-dependent and bacterial-serotype specific, and plays a pivotal role in orchestrating the functional efficiency of the innate cells and migratory characteristics of the leukocytes.


Assuntos
Comunicação Celular , Leucócitos/imunologia , Salmonella paratyphi A/imunologia , Salmonella paratyphi B/imunologia , Salmonella typhi/imunologia , Febre Tifoide/imunologia , Movimento Celular , Citocinas/análise , Células Epiteliais/imunologia , Humanos , Mucosa Intestinal/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Modelos Teóricos , Técnicas de Cultura de Órgãos
2.
Fish Shellfish Immunol ; 93: 567-574, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31394161

RESUMO

HMGB2, a member of the high mobility group box family, plays an important role in host immune responses. However, the mechanism of action of HMGB2 is not well understood. Herein, a homologue from yellow catfish (Pelteobagrus fulvidraco) was cloned and named PfHMGB2. The deduced amino acid sequence of PfHMGB2 possessed a typical tripartite structure (two DNA binding boxes and an acid tail) and shared 90% identity with the predicted HMGB2 from I. punctatus. The mRNA of PfHMGB2 was widely distributed in all 11 tested tissues in healthy fish bodies and was significantly induced in the liver and head kidney when yellow catfish were injected with inactivated Aeromonas hydrophila. Consistently, PfHMGB2 mRNA could also be induced in yellow catfish peripheral blood leucocytes (PBL) by lipopolysaccharide. The recombinant PfHMGB2 protein was purified from E. coli BL21 (DE3):pET-28a/PfHMGB2 and showed DNA-binding affinity. Moreover, rPfHMGB2 improved the phagocytosis and proliferation activity and upregulated the mRNA expression of the pro-inflammatory cytokine TNFα in yellow catfish PBL. These results indicated that PfHMGB2 could protect yellow catfish from pathogen infection by activating PBL.


Assuntos
Peixes-Gato/genética , Peixes-Gato/imunologia , Doenças dos Peixes/imunologia , Regulação da Expressão Gênica/imunologia , Proteína HMGB2/genética , Proteína HMGB2/imunologia , Imunidade Inata/genética , Aeromonas hydrophila/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Perfilação da Expressão Gênica/veterinária , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Proteína HMGB2/química , Leucócitos/imunologia , Fagocitose/imunologia , Filogenia , Alinhamento de Sequência/veterinária
3.
Nat Commun ; 10(1): 3686, 2019 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-31417080

RESUMO

In vivo liposomes, like other types of nanoparticles, acquire a totally new 'biological identity' due to the formation of a biomolecular coating known as the protein corona that depends on and modifies the liposomes' synthetic identity. The liposome-protein corona is a dynamic interface that regulates the interaction of liposomes with the physiological environment. Here we show that the biological identity of liposomes is clearly linked to their sequestration from peripheral blood mononuclear cells (PBMCs) of healthy donors that ultimately leads to removal from the bloodstream. Pre-coating liposomes with an artificial corona made of human plasma proteins drastically reduces capture by circulating leukocytes in whole blood and may be an effective strategy to enable prolonged circulation in vivo. We conclude with a critical assessment of the key concepts of liposome technology that need to be reviewed for its definitive clinical translation.


Assuntos
Leucócitos Mononucleares/imunologia , Lipossomos/sangue , Lipossomos/imunologia , Coroa de Proteína/imunologia , Adsorção , Proteínas Sanguíneas/imunologia , Proteínas Sanguíneas/metabolismo , Cromatografia Líquida de Alta Pressão , Citometria de Fluxo , Humanos , Leucócitos/imunologia , Lipossomos/metabolismo , Lipossomos/ultraestrutura , Microscopia Eletrônica de Transmissão , Coroa de Proteína/metabolismo , Espectrometria de Massas por Ionização por Electrospray , Células THP-1
4.
Fish Shellfish Immunol ; 93: 612-622, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31408730

RESUMO

In teleost fish, IgM+ B cells play important roles in innate and adaptive immunity. Different IgM+ B cells are detected in teleost, named IgMlo and IgMhi B cell subsets, according to the distinct expression levels of membrane IgM (mIgM). However, the study on the heterogeneity in IgM+ B cell subsets remains poorly understood. In this study, the comparative transcriptomic profiles of IgM-, IgMlo and IgMhi from peripheral blood of Nile tilapia (Oreochromis niloticus) were carried out by using RNA-sequencing technique. A total of 6045 and 5470 differentially expressed genes (DEGs) were detected in IgMlo and IgMhi cells, respectively, as compared with IgM- lymphocytes, whereas 3835 genes were differentially expressed when IgMlo compared to IgMhi cells. Analysis of the KEGG database indicated that the DEGs were enriched in immune system categories and signaling transduction and interaction in IgM- vs IgMhi, IgM- vs IgMlo and IgMlo vs IgMhi. Comparatively, in IgMlo vs IgMhi, GO enrichment analysis indicated that the DEGs enriched in nucleic acid binding transcription factor activity. Analysis of crucial transcription factors for B cell differentiation indicated that IgMlo and IgMhi cell clusters belonged to the different B cell subsets. The data generated in this study may provide insights into understanding the heterogeneity of IgM+ cells in teleost, and suggest that IgM+ B cells play a crucial role in innate immunity.


Assuntos
Ciclídeos/genética , Ciclídeos/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Imunidade Inata/genética , Imunoglobulina M/imunologia , Transcrição Genética/imunologia , Animais , Perfilação da Expressão Gênica/veterinária , Imunoglobulina M/genética , Leucócitos/imunologia , /veterinária
5.
J Immunol Res ; 2019: 2180409, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31396541

RESUMO

The primary purpose of pulmonary ventilation is to supply oxygen (O2) for sustained aerobic respiration in multicellular organisms. However, a plethora of abiotic insults and airborne pathogens present in the environment are occasionally introduced into the airspaces during inhalation, which could be detrimental to the structural integrity and functioning of the respiratory system. Multiple layers of host defense act in concert to eliminate unwanted constituents from the airspaces. In particular, the mucociliary escalator provides an effective mechanism for the continuous removal of inhaled insults including pathogens. Defects in the functioning of the mucociliary escalator compromise the mucociliary clearance (MCC) of inhaled pathogens, which favors microbial lung infection. Defective MCC is often associated with airway mucoobstruction, increased occurrence of respiratory infections, and progressive decrease in lung function in mucoobstructive lung diseases including cystic fibrosis (CF). In this disease, a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene results in dehydration of the airway surface liquid (ASL) layer. Several mice models of Cftr mutation have been developed; however, none of these models recapitulate human CF-like mucoobstructive lung disease. As an alternative, the Scnn1b transgenic (Scnn1b-Tg+) mouse model overexpressing a transgene encoding sodium channel nonvoltage-gated 1, beta subunit (Scnn1b) in airway club cells is available. The Scnn1b-Tg+ mouse model exhibits airway surface liquid (ASL) dehydration, impaired MCC, increased mucus production, and early spontaneous pulmonary bacterial infections. High morbidity and mortality among mucoobstructive disease patients, high economic and health burden, and lack of scientific understanding of the progression of mucoobstruction warrants in-depth investigation of the cause of mucoobstruction in mucoobstructive disease models. In this review, we will summarize published literature on the Scnn1b-Tg+ mouse and analyze various unanswered questions on the initiation and progression of mucobstruction and bacterial infections.


Assuntos
Obstrução das Vias Respiratórias/imunologia , Obstrução das Vias Respiratórias/fisiopatologia , Fibrose Cística/imunologia , Fibrose Cística/fisiopatologia , Modelos Animais de Doenças , Canais Epiteliais de Sódio/genética , Obstrução das Vias Respiratórias/metabolismo , Obstrução das Vias Respiratórias/microbiologia , Animais , Fibrose Cística/genética , Fibrose Cística/microbiologia , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Desidratação/metabolismo , Desidratação/fisiopatologia , Canais Iônicos/deficiência , Canais Iônicos/genética , Leucócitos/imunologia , Pulmão/imunologia , Pulmão/fisiopatologia , Macrófagos/imunologia , Camundongos , Camundongos Transgênicos , Depuração Mucociliar/genética , Depuração Mucociliar/imunologia , Infecções Respiratórias/imunologia , Infecções Respiratórias/fisiopatologia
6.
Int J Mol Sci ; 20(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443389

RESUMO

Alcohol exerts significant immunomodulatory effects on innate and adaptive immune responses, impairing host defense against infections. Gut-mucosa-derived dendritic cells (DCs) traffic to mesenteric lymph nodes (MLNs) through mesenteric lymphatic vessels (MLVs), contributing to intestinal antigen homeostasis. Previously, we demonstrated that acute alcohol administration to male rats induces MLV hyperpermeability resulting in perilymphatic adipose tissue (PLAT) inflammation and insulin signaling dysregulation. We hypothesized that alcohol-induced MLV hyperpermeability can lead to DC leakage to PLAT. DCs promote adipose tissue regulatory T cell (Treg) expansion, and this has been proposed as a mechanism underlying age-associated insulin resistance (IR). The aim of this study was to determine whether chronic alcohol consumption promotes DC leakage to PLAT and results in metabolic dysregulation. Male rats received a Lieber-DeCarli liquid diet containing 36% of calories from alcohol for 10 weeks. Time-matched control animals were pair-fed. PLAT, MLNs, and peripheral blood leukocytes (PBLs) were isolated for flow cytometry analyses. PLAT explants were used for determinations of insulin-induced glucose uptake. Chronic alcohol consumption decreased MLN CD4/CD8 ratio and Treg frequency in PBLs. Alcohol increased the frequency of DCs, CD4 T cells, and Tregs in PLAT. Lastly, alcohol decreased insulin-stimulated glucose uptake in PLAT. Collectively, these findings suggest that alcohol-induced immune cell deviation from the gut-MLN pathway is associated with PLAT immunometabolic dysregulation. Whether this immune cell deviation impacts induction of mucosal immunity warrants further investigation.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Etanol/farmacologia , Vasos Linfáticos/efeitos dos fármacos , Vasos Linfáticos/metabolismo , Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/imunologia , Tecido Adiposo/metabolismo , Consumo de Bebidas Alcoólicas , Animais , Relação CD4-CD8 , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Metabolismo Energético/efeitos dos fármacos , Imunomodulação/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucócitos/metabolismo , Masculino , Ratos , Circulação Esplâncnica , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
7.
Dokl Biochem Biophys ; 486(1): 201-205, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31367821

RESUMO

Infection of mice with influenza A viruses led to the formation of clones of lymphocytes that specifically recognizes viral domains in the central zone of the NSP protein (amino acid positions 83-119). Computer analysis of the primary structure of the NSP protein showed the presence of T-cell epitopes in the central part of the NSP molecule. The findings indicate that the viral NSP gene is expressed in the infected animals and verify the concept of the bipolar strategy (ambisense strategy) of the influenza A virus genome.


Assuntos
Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/fisiologia , Leucócitos/imunologia , RNA Viral/genética , Proteínas Virais/genética , Sequência de Aminoácidos , Animais , Leucócitos/virologia , Camundongos , Camundongos Endogâmicos BALB C , Domínios Proteicos , Proteínas Virais/química , Proteínas Virais/metabolismo
8.
Fish Shellfish Immunol ; 93: 631-640, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31377431

RESUMO

Fish aquaculture is the world's fastest growing food production industry and infectious diseases are a major limiting factor. Vaccination is the most appropriate method for controlling infectious diseases and a key reason for the success of salmonid cultivation and has reduced the use of antibiotics. The development of fish vaccines requires the use of a great number of experimental animals that are challenged with virulent pathogens. In vitro cell culture systems have the potential to replace in vivo pathogen exposure for initial screening and testing of novel vaccine candidates/preparations, and for batch potency and safety tests. PBL contain major immune cells that enable the detection of both innate and adaptive immune responses in vitro. Fish PBL can be easily prepared using a hypotonic method and is the only way to obtain large numbers of immune cells non-lethally. Distinct gene expression profiles of innate and adaptive immunity have been observed between bacterins prepared from different bacterial species, as well as from different strains or culturing conditions of the same bacterial species. Distinct immune pathways are activated by pathogens or vaccines in vivo that can be detected in PBL in vitro. Immune gene expression in PBL after stimulation with vaccine candidates may shed light on the immune pathways involved that lead to vaccine-mediated protection. This study suggests that PBL are a suitable platform for initial screening of vaccine candidates, for evaluation of vaccine-induced immune responses, and a cheap alternative for potency testing to reduce animal use in aquaculture vaccine development.


Assuntos
Aquicultura/métodos , Vacinas Bacterianas/imunologia , Doenças dos Peixes/prevenção & controle , Expressão Gênica/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Oncorhynchus mykiss/genética , Oncorhynchus mykiss/imunologia , Aeromonas salmonicida/imunologia , Animais , Vacinas Bacterianas/administração & dosagem , Doenças dos Peixes/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/prevenção & controle , Técnicas In Vitro/métodos , Leucócitos/imunologia , Yersinia ruckeri/imunologia
9.
Fish Shellfish Immunol ; 93: 296-307, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352112

RESUMO

Many medicinal plants have been shown to possess biological effects, including immuno-modulatory activities on human and other mammals. However, studies about the potential mechanisms of plant extracts on the humoral and tissular immunities in fish have received less attention. This study aimed to screen the immunestimulating properties of 20 ethanol plant extracts on striped catfish Pangasianodon hypophthalmus leukocytes. The peripheral blood mononuclear cells (PBMCs) and head kidney leukocytes (HKLs) of striped catfish (50 ±â€¯5 g per fish) were stimulated at 10 and 100 µg of each plant extract per mL of cell culture medium. Several humoral immune parameters (lysozyme, complement and total immunoglobulin) were examined at 24-h post stimulation (hps). Furthermore, the responses of four cytokine genes, namely il1ß, ifrγ 2a and b, and mhc class II were assessed by quantitative real-time PCR at 6, 12, 24, and 48 hps. The results showed that lysozyme, complement as well as total immunoglobulin levels in both PBMCs and HKLs were regulated by some of the plant extracts tested in a concentration-dependent manner; some plant extracts induced the highest immune responses at the low dose (10 µg mL-1) while others were more efficient at high dose (100 µg mL-1). Among the extracts, five extracts including garlic Allium sativum L. (As), neem Azadirachta indica A. Juss (Ai), asthma-plant Euphorbia hirta L. (Eh), bhumi amla Phyllanthus amarus Schum. et Thonn (Pa), and ginger Zingiber officinale Rosc (Zo) induced significant changes in the expression of pro-inflammatory cytokine (il1ß), antiviral cytokines (ifrγ 2a and b) and adaptive immune cytokine (mhc class II) in striped catfish cells. Pa always modulated the strongest expression of the four cytokines in PBMCs and HKLs over the whole experimental period (p < 0.05), whereas Zo did not stimulate the mhc class II expression in striped catfish leukocytes throughout experimental periods. These in vitro results demonstrated that some plant extracts could differently modulate great potential immune response in fish, supporting their applications in further in vivo experiments.


Assuntos
Peixes-Gato/imunologia , Fatores Imunológicos/farmacologia , Imunomodulação , Leucócitos/imunologia , Extratos Vegetais/farmacologia , Animais , Rim Cefálico/efeitos dos fármacos , Rim Cefálico/imunologia , Fatores Imunológicos/administração & dosagem , Leucócitos/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Extratos Vegetais/administração & dosagem , Especificidade da Espécie
10.
Mol Immunol ; 114: 139-148, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31352230

RESUMO

AIM: To study the role of complement receptor 1 (CR1) for binding of Escherichia coli (E. coli) to erythrocytes, for leukocyte phagocytosis, oxidative burst and complement activation in human whole blood from a CR1 deficient (CR1D) patient and healthy controls with low, medium and high CR1 numbers. METHODS: Alexa-labelled bacteria were used to quantify erythrocyte-bound bacteria, free bacteria in plasma and phagocytosis using flow cytometry. Complement activation in plasma was measured by enzyme-linked immunosorbent assay. The CR1 numbers as well as C3bc and C4bc deposition on erythrocytes were measured by flow cytometry. Cytokines were measured using multiplex technology, and bacterial growth was measured by colony forming units. CR1 was blocked using the anti-CR1 blocking mAb 3D9. RESULTS: Approximately 85% of E. coli bound to erythrocytes after 15 min incubation in donor blood with high and medium CR1 numbers, 50% in the person with low CR1 numbers and virtually no detectable binding in the CR1D (r2 = 0.87, P < 0.0007). The number of free bacteria in plasma was inversely related to erythrocyte CR1 numbers (r2 = 0.98, P < 0.0001). E. coli-induced phagocytosis and oxidative burst were significantly enhanced by the anti-CR1 mAb 3D9 and in the CR1D and the donor with low CR1 numbers. E. coli-induced complement activation in plasma, C3bc and C4bc deposition on erythrocytes, and bacterial growth were similar in all four cases. CONCLUSIONS: CR1D and low CR1 numbers prevented E. coli binding to erythrocytes, increased free bacteria in plasma, phagocytosis and oxidative burst, but did not affect plasma or surface complement activation and bacterial growth.


Assuntos
Eritrócitos/imunologia , Escherichia coli/imunologia , Leucócitos/imunologia , Fagocitose/imunologia , Receptores de Complemento 3b/imunologia , Complexo Antígeno-Anticorpo/imunologia , Ativação do Complemento/imunologia , Eritrócitos/microbiologia , Humanos , Leucócitos/microbiologia , Explosão Respiratória/imunologia
11.
Gynecol Oncol ; 154(3): 524-530, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31353053

RESUMO

OBJECTIVE: To determine the feasibility of pharmacologic beta-adrenergic blockade in women with newly diagnosed stage II-IV epithelial ovarian cancer (EOC) throughout primary treatment. METHODS: Patients initiated propranolol prior to beginning chemotherapy or surgery. Feasibility was assessed as proportion able to complete 6 chemotherapy cycles while on adrenergic suppression. Descriptive statistics summarized surveys, and paired changes were analyzed using signed rank tests. Random-intercept Tobit models examined immune response. RESULTS: Median age was 59.9; 88.5% were stage IIIC/IV; and 38.5% underwent primary debulking. Thirty-two patients were enrolled; 3 excluded because they never took propranolol; an additional 3 didn't meet inclusion criteria, leaving 26 evaluable. Eighteen of 26 (69%), 90% credible interval (CI) of 53-81%, completed 6 chemotherapy cycles plus propranolol (an 82% posterior probability that the true proportion of success is ≥60%). Among the 23 patients with baseline and six month follow up data, overall QOL, anxiety, and depression improved (P < 0.05) and leukocyte expression of pro-inflammatory genes declined (P = 0.03) after completion of therapy. Decrease from baseline of serum IL-6 and IL-8 preceded response to chemotherapy (P < 0.0014). Change from baseline IL-10 preceded complete response. CONCLUSION: Use of propranolol during primary treatment of EOC is feasible and treatment resulted in decrease in markers of adrenergic stress response. In combination with chemotherapy, propranolol potentially results in improved QOL over baseline.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Propranolol/administração & dosagem , Antagonistas Adrenérgicos beta/administração & dosagem , Idoso , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/imunologia , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante , Citocinas/sangue , Citocinas/genética , Citocinas/imunologia , Estudos de Viabilidade , Feminino , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/imunologia , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Estudos Longitudinais , Pessoa de Meia-Idade , Terapia Neoadjuvante , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida
12.
Int J Mol Sci ; 20(14)2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31330934

RESUMO

Ischemia-reperfusion injury (IRI) plays a significant role in the pathogenesis of acute kidney injury (AKI). The complicated interaction between injured tubular cells, activated endothelial cells, and the immune system leads to oxidative stress and systemic inflammation, thereby exacerbating the apoptosis of renal tubular cells and impeding the process of tissue repair. Stem cell therapy is an innovative approach to ameliorate IRI due to its antioxidative, immunomodulatory, and anti-apoptotic properties. Therefore, it is crucial to understand the biological effects and mechanisms of action of stem cell therapy in the context of acute ischemic AKI to improve its therapeutic benefits. The recent finding that treatment with conditioned medium (CM) derived from stem cells is likely an effective alternative to conventional stem cell transplantation increases the potential for future therapeutic uses of stem cell therapy. In this review, we discuss the recent findings regarding stem cell-mediated cytoprotection, with a focus on the anti-inflammatory effects via suppression of oxidative stress and uncompromised immune responses following AKI. Stem cell-derived CM represents a favorable approach to stem cell-based therapy and may serve as a potential therapeutic strategy against acute ischemic AKI.


Assuntos
Lesão Renal Aguda/etiologia , Lesão Renal Aguda/metabolismo , Apoptose , Estresse Oxidativo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Células-Tronco/metabolismo , Lesão Renal Aguda/patologia , Lesão Renal Aguda/terapia , Animais , Estudos Clínicos como Assunto , Meios de Cultivo Condicionados/farmacologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Humanos , Inflamação , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucócitos/metabolismo , Transplante de Células-Tronco Mesenquimais , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/terapia , Células-Tronco/citologia , Resultado do Tratamento
13.
Parasitol Res ; 118(9): 2621-2633, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31300888

RESUMO

Little information is available on the effects of neonicotinoid insecticides on vertebrates. Previous work using amphibians found chronic exposure to some neonicotinoids had no detrimental effects on fitness-relevant traits. However, there is some evidence of more subtle effects of neonicotinoids on immune traits and evidence that other pesticides can suppress tadpole immunity resulting in elevated levels of parasitism in the exposed tadpoles. The objective of our study was to assess whether neonicotinoid exposure affected tadpole immunometrics and susceptibility to parasitic helminths. We assessed northern leopard frog tadpole (Lithobates pipiens) levels of parasitism and leukocyte profiles following exposure to environmentally relevant concentrations of clothianidin and free-living infective cercariae of a helminth parasite, an Echinostoma sp. trematode. When comparing tadpoles from controls to either 1 or 100 µg/L clothianidin treatments, we found similar measures of parasitism (i.e. prevalence, abundance and intensity of echinostome cysts) and similar leukocyte profiles. We also confirmed that clothianidin was not lethal for cercariae; however, slight reductions in swimming activity were detected at the lowest exposure concentration of 0.23 µg/L. Our results show that exposure to clothianidin during the larval amphibian stage does not affect leukocyte profiles or susceptibility to parasitism by larval trematodes in northern leopard frogs although other aspects such as length of host exposure require further study.


Assuntos
Echinostoma/fisiologia , Equinostomíase/veterinária , Guanidinas/farmacologia , Inseticidas/farmacologia , Larva/imunologia , Neonicotinoides/farmacologia , Rana pipiens/parasitologia , Tiazóis/farmacologia , Animais , Cercárias/efeitos dos fármacos , Cercárias/crescimento & desenvolvimento , Echinostoma/efeitos dos fármacos , Echinostoma/crescimento & desenvolvimento , Equinostomíase/parasitologia , Larva/efeitos dos fármacos , Larva/parasitologia , Leucócitos/imunologia , Rana pipiens/imunologia
14.
Immunology ; 158(1): 47-59, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31315156

RESUMO

During probing and blood feeding, haematophagous mosquitoes inoculate a mixture of salivary molecules into their vertebrate hosts' skin. In addition to the anti-haemostatic and immunomodulatory activities, mosquito saliva also triggers acute inflammatory reactions, especially in sensitized hosts. Here, we characterize the oedema and the cellular infiltrate following Aedes aegypti mosquito bites in the skin of sensitized and non-sensitized BALB/c mice by flow cytometry. Ae. aegypti bites induced an increased oedema in the ears of both non-sensitized and salivary gland extract- (SGE-)sensitized mice, peaking at 6 hr and 24 hr after exposure, respectively. The quantification of the total cell number in the ears revealed that the cellular recruitment was more robust in SGE-sensitized mice than in non-sensitized mice, and the histological evaluation confirmed these findings. The immunophenotyping performed by flow cytometry revealed that mosquito bites were able to produce complex changes in cell populations present in the ears of non-sensitized and SGE-sensitized mice. When compared with steady-state ears, the leucocyte populations significantly recruited to the skin after mosquito bites in non-sensitized and sensitized mice were eosinophils, neutrophils, monocytes, inflammatory monocytes, mast cells, B-cells and CD4+ T-cells, each one with its specific kinetics. The changes in the absolute number of cells suggested two cell recruitment profiles: (i) a saliva-dependent migration; and (ii) a migration dependent on the immune status of the host. These findings suggest that mosquito bites influence the skin microenvironment by inducing differential cell migration, which is dependent on the degree of host sensitization to salivary molecules.


Assuntos
Aedes/imunologia , Quimiotaxia de Leucócito , Edema/imunologia , Mordeduras e Picadas de Insetos/imunologia , Leucócitos/imunologia , Mastócitos/imunologia , Saliva/imunologia , Pele/imunologia , Animais , Microambiente Celular , Modelos Animais de Doenças , Feminino , Cinética , Masculino , Camundongos Endogâmicos BALB C , Infiltração de Neutrófilos
15.
Vet Immunol Immunopathol ; 213: 109885, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307670

RESUMO

Protec™ is a commercial aquafeed (Skretting Italia) containing a combination of glucans, vitamin C, vitamin E and zinc (immune support pack). No research information concerning its capability to improve fish immune response is available, so in this study the potential immunomodulatory effects of Protec™ were investigated in rainbow trout (Oncorhynchus mykiss). Head kidney (HK) leukocytes from adult fish (100 g, n = 6) were in vitro incubated with Protec™ immune support pack resulting in significantly higher respiratory burst activity and proliferation. Specifically, sonicated Protec™ immune support pack (160 µg/ml) induced a respiratory burst response similar to that promoted by zymosan and lipopolysaccharide (LPS), while non-sonicated Protec™ immune support pack induced a response comparable to that of cells stimulated with phorbol myristate acetate (PMA). Moreover, the proliferation of leukocytes exposed to sonicated Protec™ immune support pack (20 µg/ml) was significantly higher than that of cells stimulated with zymosan, and it was comparable to the proliferation of cells stimulated with phytohaemagglutinin (PHA) and LPS. Afterwards, a feeding trial was performed in a rainbow trout farm. Two groups of juvenile rainbow trout (10 g) were acclimated for 7 weeks before the experiment and fed daily with a commercial control diet (Optiline HE, Skretting Italia) at 2% BW/day. At the end of acclimation, one group of fish was fed with Protec™ diet (Skretting Italia) at 2% BW/day whereas the other group continued to feed the control diet at the same level for further 4 weeks. Then, fish were sampled (HK leukocytes from n = 6 fish/group, serum from n = 12 fish/group) or intraperitoneally vaccinated against lactococcosis (n = 160/dietary group/time point). Fish fed the same diets for further 4 weeks after vaccination, then feeding returned to the control diet in both groups until the end of the trial. The specific antibody response was recorded at 4 and 8 weeks after vaccination (n = 12 fish/group). The administration of Protec™ significantly enhanced the respiratory burst activity of leukocytes and the synthesis of specific IgM against Lactococcus garvieae, whereas the serum lysozyme activity was unaffected. The present research suggests that the administration of Protec™ can improve both innate and adaptive immune response of rainbow trout, proving to be an interesting strategy for enhancing the immune reactivity of fish to vaccines.


Assuntos
Ração Animal , Anticorpos Antibacterianos/sangue , Infecções por Bactérias Gram-Positivas/veterinária , Imunidade Inata , Lactococcus , Oncorhynchus mykiss/imunologia , Imunidade Adaptativa , Adjuvantes Imunológicos/administração & dosagem , Animais , Proliferação de Células , Dieta/veterinária , Feminino , Doenças dos Peixes/imunologia , Infecções por Bactérias Gram-Positivas/imunologia , Imunoglobulina M/sangue , Leucócitos/imunologia , Oncorhynchus mykiss/microbiologia , Explosão Respiratória
16.
J Immunol Res ; 2019: 3128010, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31263712

RESUMO

Successful pregnancy requires a tightly-regulated equilibrium of immune cell interactions at the maternal-fetal interface (i.e., the decidual tissues), which plays a central role in the inflammatory process of labor. Most of the innate immune cells in this compartment have been well characterized; however, adaptive immune cells are still under investigation. Herein, we performed immunophenotyping of the decidua basalis and decidua parietalis to determine whether exhausted and senescent T cells are present at the maternal-fetal interface and whether the presence of pathological (i.e., preterm) or physiological (i.e., term) labor and/or placental inflammation alter such adaptive immune cells. In addition, decidual exhausted T cells were sorted to test their functional status. We found that (1) exhausted and senescent T cells were present at the maternal-fetal interface and predominantly expressed an effector memory phenotype, (2) exhausted CD4+ T cells increased in the decidua parietalis as gestational age progressed, (3) exhausted CD4+ and CD8+ T cells decreased in the decidua basalis of women who underwent labor at term compared to those without labor, (4) exhausted CD4+ T cells declined with the presence of placental inflammation in the decidua basalis of women with preterm labor, (5) exhausted CD8+ T cells decreased with the presence of placental inflammation in the decidua basalis of women who underwent labor at term, (6) both senescent CD4+ and CD8+ T cells declined with the presence of placental inflammation in the decidua basalis of women who underwent preterm labor, and (7) decidual exhausted T cells produced IFNγ and TNFα upon in vitro stimulation. Collectively, these findings indicate that exhausted and senescent T cells are present at the human maternal-fetal interface and undergo alterations in a subset of women either with labor at term or preterm labor and placental inflammation. Importantly, decidual T cell function can be restored upon stimulation.


Assuntos
Trabalho de Parto/imunologia , Troca Materno-Fetal/imunologia , Trabalho de Parto Prematuro/imunologia , Placenta/imunologia , Linfócitos T/imunologia , Adulto , Biomarcadores , Senescência Celular/imunologia , Decídua/imunologia , Decídua/metabolismo , Feminino , Humanos , Imunofenotipagem , Trabalho de Parto/metabolismo , Leucócitos/imunologia , Leucócitos/metabolismo , Contagem de Linfócitos , Trabalho de Parto Prematuro/metabolismo , Placenta/metabolismo , Gravidez , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T/metabolismo , Adulto Jovem
17.
Int J Mol Sci ; 20(14)2019 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-31336833

RESUMO

Leukocyte infiltration is a hallmark of inflammatory responses. This process depends on the bacterial and host tissue-derived chemotactic factors interacting with G-protein-coupled seven-transmembrane receptors (GPCRs) expressed on the cell surface. Formylpeptide receptors (FPRs in human and Fprs in mice) belong to the family of chemoattractant GPCRs that are critical mediators of myeloid cell trafficking in microbial infection, inflammation, immune responses and cancer progression. Both murine Fprs and human FPRs participate in many patho-physiological processes due to their expression on a variety of cell types in addition to myeloid cells. FPR contribution to numerous pathologies is in part due to its capacity to interact with a plethora of structurally diverse chemotactic ligands. One of the murine Fpr members, Fpr2, and its endogenous agonist peptide, Cathelicidin-related antimicrobial peptide (CRAMP), control normal mouse colon epithelial growth, repair and protection against inflammation-associated tumorigenesis. Recent developments in FPR (Fpr) and ligand studies have greatly expanded the scope of these receptors and ligands in host homeostasis and disease conditions, therefore helping to establish these molecules as potential targets for therapeutic intervention.


Assuntos
Fatores Quimiotáticos/metabolismo , Receptores de Formil Peptídeo/metabolismo , Sequência de Aminoácidos , Animais , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Quimiotaxia , Quimiotaxia de Leucócito/imunologia , Descoberta de Drogas , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Leucócitos/imunologia , Leucócitos/metabolismo , Ligantes , Peptídeos/química , Peptídeos/metabolismo , Receptores de Formil Peptídeo/agonistas , Receptores Acoplados a Proteínas-G/agonistas , Receptores Acoplados a Proteínas-G/metabolismo , Transdução de Sinais , Proteínas Virais/química , Proteínas Virais/metabolismo
18.
J Neuroinflammation ; 16(1): 137, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277647

RESUMO

BACKGROUND: The lack of effective treatment for Alzheimer's disease (AD) stems mainly from the incomplete understanding of AD causes. Neuroinflammation has emerged as an important component of AD pathology, and a vast number of experimental and clinical data indicated a crucial role for the activation of the innate immune system in disease promotion and symptom progression. METHODS: Clinical examinations of AD patients in a different stage of disease severity in correlation with the measurement of two innate immune reactions, i.e., peripheral blood leukocyte (PBLs) resistance to viral infection (vesicular stomatitis virus, VSV) ex vivo, and cytokines: TNF-α, IFN-γ, IL-1ß, and IL-10, production with enzyme-linked immunosorbent assay (ELISA), have been investigated during this preliminary study before and after 4 weeks of oral treatment with dietary supplement proline-rich polypeptide complex (PRP) (120 µg of PRP/day). The potential effect of PRP on the distribution of PBLs' subpopulations has been specified. RESULTS: We have found a deficiency in innate immune response in AD patients. It was demonstrated for the first time that the degree of PBLs resistance to VSV infection was closely related to the stage of clinical severity of AD. Our study showed significant differences in cytokine production which pointed that in AD patients innate immune mechanisms are impaired. Administration of PRP to our patients increased innate immune response of PBLs and declined pro- and anti-inflammatory cytokine production, thus subduing the excessively developed inflammatory response, especially among patients with high severity of AD. PRP did not exhibit a pro-proliferative activity. It was showed, however, significant influence of PRP on the distribution of PBLs' subpopulations. CONCLUSION: The findings mentioned above might be crucial in the context of potential application of immunomodulatory therapy in AD patients and indicated PRP as a potential target for future treatments in neuroinflammatory diseases like AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/imunologia , Imunidade Inata/efeitos dos fármacos , Receptores de Peptídeos/administração & dosagem , Receptores de Peptídeos/imunologia , Adulto , Idoso , Doença de Alzheimer/metabolismo , Animais , Linhagem Celular , Citocinas/antagonistas & inibidores , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Humanos , Imunidade Inata/fisiologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucócitos/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Domínios Proteicos Ricos em Prolina/efeitos dos fármacos , Domínios Proteicos Ricos em Prolina/fisiologia , Receptores de Peptídeos/metabolismo
19.
Fish Shellfish Immunol ; 93: 174-182, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302286

RESUMO

The present study was aimed to evaluate the effects of the cyclophosphamide (CY) exposure (Control, 0.032, 0.32, 1.0, 1.6 and 3.2 mg/mL) on the damage in the peripheral blood leukocytes of blunt snout bream for 24 h, which including cell viability, apoptosis, lactate dehydrogenase (LDH) release, mitochondrial membrane potential (Δѱm), ROS, antioxidant enzyme activity and the relative mRNA levels of apoptosis. Results showed that cell viability and Δѱm effects of CY were greatly reduced, and occurred in a dose-dependent manner. CY exposure (0.32-3.2 mg/mL) significantly increased the LDH release and induced apoptosis accompanied by ΔΨm disruption and ROS generation compared to the control. The cellular ROS was significantly increased with increase of CY level from 0.032 mg/mL to 1 mg/mL and the plateau occurred at 0.32 mg/mL. Additionally CY exposure led to oxidative stress as evidenced by significantly the decrease of SOD and CAT and increase of MDA concentration after treating cells with 3.2 mg/mL of CY. Besides, the relative mRNA levels of caspase-3 in the dose of 0.032, 0.32 mg/mL CY, caspase-9 and interleukins-1ß (IL-1ß) in the dose of 0.32 mg/mL CY, tumor necrosis factor-alpha (TNF-α) in the dose of 0.032 mg/mL CY significantly higher than that of the control. In conclusion, 0.32-3.2 mg/mL CY could lead to cytotoxic effect, inflammatory response and induce the apoptosis of the peripheral blood leukocyte of Megalobrama amblycephala.


Assuntos
Apoptose/efeitos dos fármacos , Ciclofosfamida/toxicidade , Cyprinidae/imunologia , Citotoxinas/toxicidade , Inflamação/veterinária , Estresse Oxidativo/efeitos dos fármacos , Animais , Antineoplásicos/toxicidade , Cyprinidae/fisiologia , Doenças dos Peixes/induzido quimicamente , Doenças dos Peixes/imunologia , Inflamação/induzido quimicamente , Inflamação/imunologia , Leucócitos/imunologia , Poluentes Químicos da Água/toxicidade
20.
Mediators Inflamm ; 2019: 4123605, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205449

RESUMO

Leukocyte recruitment is a hallmark of the inflammatory response. Migrating leukocytes breach the endothelium along with the vascular basement membrane and associated pericytes. While much is known about leukocyte-endothelial cell interactions, the mechanisms and role of pericytes in extravasation are poorly understood and the classical paradigm of leukocyte recruitment in the microvasculature seldom adequately discusses the involvement of pericytes. Emerging evidence shows that pericytes are essential players in the regulation of leukocyte extravasation in addition to their functions in blood vessel formation and blood-brain barrier maintenance. Junctions between venular endothelial cells are closely aligned with extracellular matrix protein low expression regions (LERs) in the basement membrane, which in turn are aligned with gaps between pericytes. This forms preferential paths for leukocyte extravasation. Breaching of the layer formed by pericytes and the basement membrane entails remodelling of LERs, leukocyte-pericyte adhesion, crawling of leukocytes on pericyte processes, and enlargement of gaps between pericytes to form channels for migrating leukocytes. Furthermore, inflamed arteriolar and capillary pericytes induce chemotactic migration of leukocytes that exit postcapillary venules, and through direct pericyte-leukocyte contact, they induce efficient interstitial migration to enhance the immunosurveillance capacity of leukocytes. Given their role as regulators of leukocyte extravasation, proper pericyte function is imperative in inflammatory disease contexts such as diabetic retinopathy and sepsis. This review summarizes research on the molecular mechanisms by which pericytes mediate leukocyte diapedesis in inflamed tissues.


Assuntos
Leucócitos/metabolismo , Pericitos/metabolismo , Animais , Membrana Basal/imunologia , Membrana Basal/metabolismo , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/metabolismo , Humanos , Inflamação/imunologia , Inflamação/metabolismo , Leucócitos/imunologia , Pericitos/imunologia
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