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1.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(7): 577-582, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31537240

RESUMO

Objective To investigate the roles of Th1 cytokines tumor necrosis factor α (TNF-α), interferon gamma (IFN-γ) and multifunctional T cells in nucleotides binding oligomer domain 2 knockout (NOD2-/-) mice infected with Mycobacterium tuberculosis (MTB) H37Ra. Methods Mouse models of pulmonary infection were established by tracheal instillation of MTB strain H37Ra into NOD2-/- mice and C57BL/6 mice (n=10 each group). Lung tissues were removed and stained by HE staining and pathological scores were evaluated 4 weeks after infection. The levels of TNF-α and IFN-γ in the lung homogenates were detected by ELISA, and the ratio of multifunctional CD4+ T and CD8+ T cells in the spleen were examined by flow cytometry. Results MTB infection promoted lung inflammation of NOD2-/- mice. The levels of TNF-α and IFN-γ in the lung tissues of NOD2-/- mice increased. Compared with normal saline group, TNF-α+, IFN-γ+ cells and TNF-α+IFN-γ+ cells in CD4+/CD8+T cells significantly increased in NOD2-/- mice and C57BL/6 mice after the infection. TNF-α+CD4+T cells, IFN-γ+CD4+T cells and IFN-γ+CD8+T cells in MTB-infected NOD2-/- mice were significantly higher than those in MTB-infected C57BL/6 mice. Conclusion H37Ra can induce Th1 immune response in NOD2-/- mice.


Assuntos
Mycobacterium tuberculosis , Células Th1/imunologia , Tuberculose/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Interferon gama/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Adaptadora de Sinalização NOD2/genética , Baço/citologia , Baço/imunologia , Fator de Necrose Tumoral alfa/imunologia
2.
Artigo em Chinês | MEDLINE | ID: mdl-31446716

RESUMO

Summary Allergic rhinitis(AR), a common and frequente disease, has attracted global attention in recent years. The imbalance between Th1 and Th2 cellular immune responses is the immunological basis of AR. Studies have found that vitamin D plays an important role in the occurrence of AR, and IL-33/ST2 is a newly discovered cytokine and signaling pathway in AR. There are certain specific associations between vitamin D and IL-33/ST2 in the pathogenesis of AR. This paper mainly analyzes the studies on the expression of vitamin D, IL-33/ST2 and Th1/Th2 cytokines in AR, so as to clarify the role of the above two factors in the pathogenesis of AR.


Assuntos
Interleucina-33/sangue , Rinite Alérgica/sangue , Vitamina D/sangue , Citocinas/sangue , Humanos , Células Th1/imunologia , Células Th2/imunologia , Vitaminas
3.
APMIS ; 127(9): 642-652, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31274210

RESUMO

Hepatitis C virus (HCV) infection always leads to chronic hepatitis via dysregulation of host immunity. Notch signaling also modulates the response of monocytes/macrophages. Thus, we aimed to investigate the regulatory role of Notch signaling to CD14+ monocytes. Forty patients with chronic hepatitis C and twenty normal controls (NC) were enrolled. CD14+ monocytes and CD4+ T cells were purified from peripheral bloods. Notch receptors' mRNA expression in CD14+ monocytes was semi-quantified by real-time PCR. Cytokine production by CD14+ monocytes in response to γ-secretase inhibitor (GSI) was investigated by ELISA. GSI-induced CD14+ monocytes activity to HCV clearance in Huh7.5 cells and to CD4+ T cell differentiation was also assessed in direct and indirect contact co-culture system. Notch1 mRNA relative level was approximately 10-fold elevated in CD14+ monocytes from chronic hepatitis C patients when compared with NC. GSI stimulation resulted in enhanced cytokines production by CD14+ monocytes from chronic hepatitis C patients. GSI-stimulated CD14+ monocytes from chronic hepatitis C patients induced suppression of HCV RNA replication in both direct and indirect contact co-culture system of CD14+ monocytes and HCVcc-infected Huh7.5 cells, and this process was accompanied by elevation of interferon-γ production but not increased target cell death. Moreover, GSI stimulation also enhanced CD14+ monocytes-induced Th1 and Th17 cells activation, and this process required direct cell-to-cell contact. Effective antiviral therapy down-regulated Notch1 mRNA expression and promoted cytokine production by CD14+ monocytes from chronic hepatitis C. Current data revealed an important immunoregulatory property of Notch signaling to CD14+ monocytes in chronic HCV infection.


Assuntos
Hepatite C Crônica/imunologia , Monócitos/imunologia , Receptor Notch1/imunologia , Transdução de Sinais/imunologia , Adulto , Linfócitos T CD4-Positivos , Diferenciação Celular/imunologia , Técnicas de Cocultura , Regulação para Baixo/imunologia , Feminino , Hepacivirus/imunologia , Humanos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Células Th1/imunologia , Células Th17/imunologia , Adulto Jovem
4.
Exp Parasitol ; 204: 107725, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306646

RESUMO

Characterisation of the cellular immune response to schistosomiasis is well established for Schistosoma mansoni but a comprehensive description of T cell-mediated immune responses against S. japonicum infection is lacking. Accordingly, 20 CBA mice were infected with cercariae of S. japonicum and the immune response at different time points was determined. Mouse spleen and liver lymphocytes were isolated from the mice and stimulated with schistosomal adult worm antigen preparation (SWAP) and schistosomal soluble egg antigen (SEA). There was a relatively higher Th1 immune response to SWAP compared to SEA at the early phase of infection (up to week 5 post challenge). However, a Th2 immune response directed against SEA was dominant at week 6 post-infection, a time point when the highest IgG response against both SWAP and, especially, SEA was generated. The regulatory immune response was highest at the early phase of the immune response (up to week 5 post challenge) followed by a rapid decline at week 6-post infection. Before egg-laying, S. japonicum induced a regulatory T cell immune response which may limit the early Th1-mediated immune response that is believed to be protective in murine schistosomiasis. Following egg laying, the immune response was polarized to a Th2 immune response mainly directed against the eggs and this may contribute to parasite survival.


Assuntos
Imunidade Celular , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Linfócitos T/imunologia , Animais , Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interleucina-17/imunologia , Interleucina-17/metabolismo , Fígado/citologia , Fígado/imunologia , Fígado/parasitologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos CBA , Óvulo/imunologia , Contagem de Ovos de Parasitas , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Caramujos/parasitologia , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th2/imunologia
5.
Nature ; 571(7765): 403-407, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31217581

RESUMO

Activated CD4 T cells proliferate rapidly and remodel epigenetically before exiting the cell cycle and engaging acquired effector functions. Metabolic reprogramming from the naive state is required throughout these phases of activation1. In CD4 T cells, T-cell-receptor ligation-along with co-stimulatory and cytokine signals-induces a glycolytic anabolic program that is required for biomass generation, rapid proliferation and effector function2. CD4 T cell differentiation (proliferation and epigenetic remodelling) and function are orchestrated coordinately by signal transduction and transcriptional remodelling. However, it remains unclear whether these processes are regulated independently of one another by cellular biochemical composition. Here we demonstrate that distinct modes of mitochondrial metabolism support differentiation and effector functions of mouse T helper 1 (TH1) cells by biochemically uncoupling these two processes. We find that the tricarboxylic acid cycle is required for the terminal effector function of TH1 cells through succinate dehydrogenase (complex II), but that the activity of succinate dehydrogenase suppresses TH1 cell proliferation and histone acetylation. By contrast, we show that complex I of the electron transport chain, the malate-aspartate shuttle and mitochondrial citrate export are required to maintain synthesis of aspartate, which is necessary for the proliferation of T helper cells. Furthermore, we find that mitochondrial citrate export and the malate-aspartate shuttle promote histone acetylation, and specifically regulate the expression of genes involved in T cell activation. Combining genetic, pharmacological and metabolomics approaches, we demonstrate that the differentiation and terminal effector functions of T helper cells are biochemically uncoupled. These findings support a model in which the malate-aspartate shuttle, mitochondrial citrate export and complex I supply the substrates needed for proliferation and epigenetic remodelling early during T cell activation, whereas complex II consumes the substrates of these pathways, which antagonizes differentiation and enforces terminal effector function. Our data suggest that transcriptional programming acts together with a parallel biochemical network to enforce cell state.


Assuntos
Diferenciação Celular , Mitocôndrias/metabolismo , Células Th1/citologia , Células Th1/imunologia , Acetilação , Animais , Ácido Aspártico/metabolismo , Diferenciação Celular/genética , Linhagem Celular , Proliferação de Células/genética , Ácido Cítrico/metabolismo , Ciclo do Ácido Cítrico , Transporte de Elétrons , Feminino , Histonas/metabolismo , Humanos , Ativação Linfocitária/genética , Malatos/metabolismo , Masculino , Camundongos , Succinato Desidrogenase/metabolismo , Células Th1/metabolismo , Transcrição Genética
6.
Int Arch Allergy Immunol ; 180(1): 10-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31234191

RESUMO

BACKGROUND: Shrimp-derived allergen has a serious impact on people's health. Chitosan oligosaccharide (COS) has anti-allergic action but its function on shrimp allergen-induced allergy and related molecular mechanisms remain unclear. METHODS: COS and its degrees of polymerization (DP) were selected to interact with shrimp tropomyosin (TM) and IgE was measured. A mouse model of food allergy was established by receiving shrimp TM intraperitoneally. The models were treated with different concentrations of COS. Fecal and serum histamine, serum IgE, IgG1 and IgG2a, and inflammatory cytokines were measured. RESULTS: The main products for COS were DP2-6 with the contents of 6, 40, 26, 16, and 4%, respectively, and reacted with shrimp TM increasingly when COS DP was increased. Severe symptoms of food allergy were observed in the TM group (diarrhea, anaphylactic response, and rectal temperature). In contrast, COS treatment improved these symptoms significantly (p < 0.05). The sensitized mice were desensitized after they were treated with 1 mg/kg COS. COS treatment significantly reduced serum IgE and IgG1 levels, and increased IgG2a levels (p < 0.05). COS consumption decreased fecal and serum histamine. COS treatment reduced Th2 cytokine (IL-4, IL-5, and IL-13) levels and increased the Th1 cytokine (IFN-γ) level (p < 0.05). CONCLUSIONS: COS showed anti-allergy properties by regulating the levels of Th1 and Th2 cytokines.


Assuntos
Alérgenos/imunologia , Antialérgicos/farmacologia , Quitosana , Crustáceos , Hipersensibilidade Alimentar/imunologia , Oligossacarídeos/farmacologia , Células Th1/imunologia , Células Th2/imunologia , Tropomiosina/imunologia , Animais , Antialérgicos/química , Quitosana/química , Citocinas/metabolismo , Modelos Animais de Doenças , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/metabolismo , Liberação de Histamina/efeitos dos fármacos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Camundongos , Oligossacarídeos/química , Fenótipo , Células Th1/metabolismo , Células Th2/metabolismo
7.
Scand J Immunol ; 90(3): e12799, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31211854

RESUMO

Pemphigus vulgaris (PV) is an autoimmune disease characterized by the production of IgG autoantibodies owing to an imbalance in the Th1/Th2 and Th17/Tregs cell pathways. The role of gut microbiota in the development of immune system and autoimmune diseases has been unraveled in the last two decades. However, data pertaining to gut microbiota of PV patients is largely lacking. We aimed to compare the gut microbiota of PV patients and healthy controls and assessed potential correlation with circulating cytokines of Th1/Th2/Th17 cell. Faecal bacterial diversity was analysed in 18 PV patients and 14 age- and gender-matched healthy individuals using hypervariable tag sequencing of the V3-V4 region of the 16S rRNA gene. Plasma levels of 20 inflammatory cytokines were assessed using the Luminex screening system. As a result, we identified 10 differentially abundant taxa between patients and controls. At the genera level, Lachnospiracea_incertae_sedis and Coprococcus decreased, while Granulicatella, Flavonifractor enriched in PV. Plasma levels of C5a, interleukin (IL)-2R, IL-6, IL-8, IL-7, IL-1ß, IL17A, IL-5 and IL-21 were significantly increased in PV Flavonifractor exhibited a positive correlation with C5a, IL-6, IL-8, IL-7, IL-1ß, IL17A and IL-21. Lachnospiracea_incertae_sedis and Coprococcus showed a negative correlation with IL-17A. Our results are consistent with the hypothesis that PV patients have gut microbial dysbiosis which might contribute to the immune disorder and the development of PV.


Assuntos
Doenças Autoimunes/imunologia , Citocinas/imunologia , Microbioma Gastrointestinal/imunologia , Inflamação/imunologia , Pênfigo/imunologia , Plasma/imunologia , Adulto , Autoanticorpos/imunologia , Doenças Autoimunes/microbiologia , Fezes/microbiologia , Feminino , Humanos , Inflamação/microbiologia , Masculino , Pessoa de Meia-Idade , Pênfigo/microbiologia , Plasma/microbiologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/microbiologia , Células Th1/imunologia , Células Th1/microbiologia , Células Th17/imunologia , Células Th17/microbiologia , Células Th2/imunologia , Células Th2/microbiologia
8.
Future Microbiol ; 14: 705-716, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31161794

RESUMO

Aim: Aspergillus fumigatus is one of the most common opportunistic fungi that can cause invasive infection. To profile the kinetic variation of immune cells and cytokines after exposure to A. fumigatus thoroughly, we established a pulmonary A. fumigatus infection model in temporarily immunosuppressed mice. Materials & methods: Systematic and kinetic studies of different immune cells and cytokines were performed. Results: We observed that the granulocytes and macrophages recruited to the site of infection played an important role in the infectious phase. There was a significant increase in the cytokines IFN-γ, IL-6, TNF-α as well as the chemokines CXCL1, MIP-1α, MIP-2 and CCL5 after infection. IL-10 was found to participate in balancing the anti-inflammatory response in the recovery phases. The immune response mediated by T cells was mainly presented by the Th1-type on day 7 after exposure with a high proportion of IFN-γ+ CD4+ T cells and CD4+CD44highCD62Llow effector T cells. Conclusion: These kinetic parameters of the immune response might provide diagnostic clues for A. fumigatus infection.


Assuntos
Aspergilose/imunologia , Aspergillus fumigatus/patogenicidade , Quimiocinas/metabolismo , Citocinas/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Animais , Linfócitos T CD4-Positivos , Quimiocina CCL3/metabolismo , Quimiocina CCL5/metabolismo , Quimiocina CXCL1/metabolismo , Quimiocina CXCL2/metabolismo , Quimiocinas/sangue , Citocinas/sangue , Modelos Animais de Doenças , Hospedeiro Imunocomprometido , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Cinética , Pulmão/microbiologia , Pulmão/patologia , Linfonodos/microbiologia , Linfonodos/patologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Linfócitos T/imunologia , Células Th1/imunologia , Fator de Necrose Tumoral alfa/metabolismo
9.
World J Microbiol Biotechnol ; 35(6): 91, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161259

RESUMO

The limited efficacy of available influenza vaccines against rapidly emerging new viral strains stresses the need for the development of new antigen-independent prophylactic treatment for enhancing immunity against influenza infection. Recent studies suggest that probiotics possess immunomodulatory properties and can reduce the severity of respiratory infections. Here, we investigated the potential of prophylactic Bifidobacterium bifidum in improving anti-influenza immune responses in an experimental lethal mouse-adapted influenza A (H1N1) infection in a BALB/c mouse model. One week after viral challenge, splenocyte proliferation assay (MTT), IFN-gamma, IL-12, and IL-4 in spleen and IL-6 in the lung homogenates were conducted using ELISA assays. Sera samples were collected to measure IgG1 and IgG2a levels. Furthermore, the mice challenged with lethal influenza virus were assessed for survival rate. The findings demonstrated a strong induction of both humoral and cellular immunities, as well as decreased level of IL-6 production in the lung and an increase in survival rate in the mice receiving Bifidobacterium than those of the control group were observed. Taken together, the results indicate a robust potential for Bifidobacterium to modulate humoral and cellular immune responses and induce balanced Th1/Th2 immune responses against influenza infection.


Assuntos
Bifidobacterium bifidum/fisiologia , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/tratamento farmacológico , Influenza Humana/imunologia , Probióticos/farmacologia , Animais , Proliferação de Células , Citocinas/metabolismo , Modelos Animais de Doenças , Cães , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunização , Imunoglobulina G/sangue , Imunomodulação , Vírus da Influenza A Subtipo H1N1/patogenicidade , Interferon gama/metabolismo , Interleucina-12/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Pulmão/imunologia , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Baço/imunologia , Taxa de Sobrevida , Células Th1/imunologia , Células Th2/imunologia
10.
Int J Nanomedicine ; 14: 3129-3143, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31118627

RESUMO

Background: Bacillus Calmette-Guérin, the attenuated strain of Mycobacterium bovis, remains the only available vaccine against tuberculosis (TB). However, its ineffectiveness in adults against pulmonary TB and varied protective efficacy (0-80%) speak to an urgent need for the development of an improved and efficient TB vaccine. In this milieu, poly(lactic-co-glycolic acid) (PLGA), is a preferential candidate, due to such properties as biocompatibility, targeted delivery, sustained antigen release, and atoxic by-products. Methods: In this study, we formulated PLGA nanoparticles (NPs) encapsulating the bivalent H1 antigen, a fusion of Mycobacterium tuberculosis (Mtb) Ag85B and ESAT6 proteins, and investigated its role in immunomodulation and protection against Mtb challenge. Using the classical water-oil-water solvent-evaporation method, H1-NPs were prepared, with encapsulation efficiency of 86.1%±3.2%. These spherical NPs were ~244.4±32.6 nm in diameter, with a negatively charged surface (ζ-potential -4±0.6 mV). Results: Under physiological conditions, NPs degraded slowly and the encapsulated H1 antigen was released over a period of weeks. As a proof-of-concept vaccine candidate, H1 NPs were efficiently internalized by the THP-1 human macrophages. Six weeks after a single-dose vaccination, H1 NP-immunized C57BL/6J mice showed significant increase in the production of total serum IgG (P<0.0001) and its isotypes compared to H1 alone, IgG2a being the predominant one, followed by IgG1. Further, the cytokine-release profile of antigen-stimulated splenocyteculture supernatant indicated a strong TH1-biased immunoresponse in H1 NP-vaccinated mice, with ~6.03- and ~2.8-fold increase in IFNγ and TNFα cytokine levels, and ~twofold and 1.6 fold increase in IL4 and IL10 cytokines, respectively, compared to H1 alone-immunized mice. In protection studies, H1 NP-vaccinated mice displayed significant reductions in lung and spleen bacillary load (P<0.05) at 5-week post-Mtb H37Rv challenge and prolonged survival, with a mean survival time of 177 days, compared to H1 alone-vaccinated mice (mean survival time 80 days). Conclusion: Altogether, our findings highlight the significance of the H1-PLGA nanoformulation in terms of providing long-term protection in mice with a single dose.


Assuntos
Imunidade , Nanopartículas/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Proteínas Recombinantes de Fusão/metabolismo , Tuberculose/imunologia , Tuberculose/prevenção & controle , Animais , Citocinas/metabolismo , Relação Dose-Resposta Imunológica , Liberação Controlada de Fármacos , Endocitose , Epitopos , Feminino , Humanos , Imunidade Humoral , Imunização , Imunoglobulina G/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Mycobacterium tuberculosis/imunologia , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Baço/citologia , Baço/imunologia , Análise de Sobrevida , Células THP-1 , Células Th1/imunologia , Vacinas contra a Tuberculose/imunologia , Vacinação
11.
Parasitol Res ; 118(6): 1849-1863, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31055672

RESUMO

In the search for immunoprophylactics for the control of human lymphatic filariasis, we recently identified troponin 1 (Tn1) in Brugia malayi adult worms. The present study reports the cloning and expression of the B. malayi Tn1 (Tn1bm), its immunoprophylactic efficacy against B. malayi infection, and the immunological responses of the host. The Tn1bm gene was cloned (Acc no. JF912447) and expressed, and the purified recombinant Tn1bm (rTn1bm) presented a single ~ 27 kDa band. Parasite load in rTn1bm-immunized BALB/c mice challenged with B. malayi infective larvae (L3) was assessed. In rTn1bm-immunized animals, IgE, IgG, and IgG subclasses in the serum, cell proliferative response, Th1 and Th2 cytokine secretion (from splenocytes), and NO release (from peritoneal macrophages) were determined. Antibody-dependent cell-mediated cytotoxicity (ADCC) to L3 was assayed using rTn1bm-immune serum. The innate immune response markers MHC class-I, MHC class-II, TLR2, TLR4, and TLR6 expression in peritoneal macrophages and CD3+, CD4+, CD8+, and CD19+ in the splenocyte population were determined in Tn1bm-exposed cells from naïve mice. rTn1bm-immunized L3-challenged animals showed a 60% reduction in parasite burden. Immunization upregulated cellular proliferation, cytokine (IFN-γ, TNF-α, IL-1ß, IL-4, IL-6, and IL-10) secretion, NO release, and antigen-specific IgG, IgG1, and IgG2b antibody levels. rTn1bm-immune serum killed > 65% of L3 in the ADCC assay. Increased MHC class-II, TLR2, and TLR6 expression and the relative CD4+ and CD19+ cell populations of naïve animal cells indicated the ability of rTn1bm to mobilize innate immune responses. This is the first report of the immunoprophylactic potential of rTn1bm against B. malayi.


Assuntos
Anticorpos Antiprotozoários/sangue , Brugia Malayi/imunologia , Filariose Linfática/imunologia , Filariose Linfática/prevenção & controle , Troponina I/genética , Troponina I/imunologia , Animais , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Brugia Malayi/genética , Clonagem Molecular , Citocinas/sangue , Citocinas/imunologia , DNA Complementar/metabolismo , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Macrófagos Peritoneais/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Carga Parasitária , Células Th1/imunologia , Células Th2/imunologia , Vacinação
12.
Cancer Sci ; 110(7): 2100-2109, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31100180

RESUMO

The presence of interleukin (IL)-17-producing T cells has recently been reported in non-small cell lung cancer (NSCLC) patients. However, the long-term prognostic significance of these populations in NSCLC patients remains unknown. In the present study, we collected peripheral blood from 82 NSCLC patients and 22 normal healthy donors (NC). Percentages of IL-17-producing CD4+ T (Th17), CD8+ T (Tc17) and γδT cells (γδT17) were measured to determine their association with clinical outcomes and overall survival (OS) in NSCLC. All NSCLC patients were followed up until July 2018. Median follow-up time was 13.5 months (range 1-87 months). The 3- and 5-year survival rate was 27% and 19.6%, respectively. We found that Th17 cells and γδT17 cells were significantly increased, whereas Tc17 cells were markedly decreased in patients with NSCLC compared with those in NC. In addition, Th17 cells were significantly positively associated with T helper type 1 cells (Th1), whereas γδT17 cells were significantly negatively associated with γδT + interferon (IFN)-γ+ cells. High percentages of peripheral Tc17 cells were significantly associated with favorable 5-year OS (P = .025), especially in patients with early TNM stage (P = .016). Furthermore, high percentages of peripheral Th17 cells were positively associated with favorable 5-year OS in patients with late TNM stage (P = .002). However, no significant association was observed between γδT17 cells and OS, regardless of the TNM stage. In conclusion, our findings suggest that enhanced Th17 and reduced Tc17 cells in the peripheral blood could be a significant predictor of a favorable prognosis for NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Interleucina-17/metabolismo , Neoplasias Pulmonares/patologia , Linfócitos T/citologia , Células Th17/citologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Interferon gama/metabolismo , Linfócitos Intraepiteliais/citologia , Linfócitos Intraepiteliais/imunologia , Neoplasias Pulmonares/imunologia , Contagem de Linfócitos , Masculino , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Linfócitos T/imunologia , Células Th1/citologia , Células Th1/imunologia , Células Th17/imunologia
13.
Iran J Allergy Asthma Immunol ; 18(2): 163-172, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31066252

RESUMO

Unexplained infertility (UI) is one of the most common diagnoses in the fertility care. Seminal plasma (SP) plays a crucial role in the regulation of female immune responses and the success of a pregnancy. In vitro fertilization (IVF) is a well-known method for the treatment of UI. In this study, we aimed to investigate the effect of SP on the differentiation of T helper (Th) cell subsets and the relationship between these subsets with the rate of IVF success in a group of women complicated with UI compared to those with normal pregnancy. This study was conducted on 20 UI couples (ten with successful and ten with unsuccessful IVF outcome) and 10 fertile couples as the control group. Four color flow cytometry technique was used to detect Th cell subsets in the peripheral blood mononuclear cells (PBMC) with or without stimulation by SP. Results indicated that the frequencies of IL-17+ and Foxp3+ T cells after incubation with SP was significantly increased in couples with unsuccessful IVF outcome as compared to successful and healthy groups (p<0.05). Additionally, a positive correlation was observed between Th1 and Th2 cells in the unsuccessful IVF group (R=0.6, p=0.03). In summary, the results of the present study demonstrated that exposure to SP might increase Th17 and Treg cell frequencies in infertile women with unsuccessful IVF, and might also balance inflammatory to regulatory responses to finally tune-up the Th1/Th2/Th17/Treg balance and support the success of IVF.


Assuntos
Fertilização In Vitro/métodos , Infertilidade Feminina/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Adulto , Biomarcadores , Células Cultivadas , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imunofenotipagem , Infertilidade Feminina/diagnóstico , Interleucina-17/metabolismo , Masculino , Prognóstico , Sêmen/metabolismo , Resultado do Tratamento
14.
Blood Coagul Fibrinolysis ; 30(4): 133-139, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31090595

RESUMO

: An increased T-helper cell (Th) 1/Th2 ratio in the peripheral blood has been proposed to correlate with the disease activity of immune thrombocytopenia (ITP). T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) is a Th1-associated cell surface molecule that regulates Th1 responses and promotes tolerance. Consequently, we aimed to determine whether the regulation of TIM-3 expression is likely to be a promising therapeutic approach for ITP. In the present study, we investigated the immunomodulatory activities of TIM-3 in human peripheral blood mononuclear cell (PBMC) cultures. Levels of interferon-gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-4, IL-5, IL-2, and IL-10 were determined in PBMCs from 11 ITP patients and 10 healthy patients after TIM-3 antibody administration for 48 h. The proliferation of PBMCs was examined by cell counting kit-8 assay. Flow cytometry was used to observe apoptosis by staining cells with annexin V-fluorescein isothiocyanate/propidine iodide. PBMCs from ITP patients secreted higher amounts of IFN-γ than those from control patients but paradoxically expressed lower levels of TIM-3. Depletion of TIM-3 in PBMCs in vitro using a TIM-3 antibody enhanced IFN-γ secretion, directly demonstrating that TIM-3 expression on human T cells regulates proliferation and IFN-γ secretion. Failure to upregulate the T-cell expression of TIM-3 may represent a novel intrinsic defect that contributes to the pathogenesis of ITP.


Assuntos
Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Púrpura Trombocitopênica Idiopática/terapia , Células Th1/imunologia , Apoptose , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Regulação da Expressão Gênica , Receptor Celular 2 do Vírus da Hepatite A/antagonistas & inibidores , Humanos , Leucócitos Mononucleares/citologia , Púrpura Trombocitopênica Idiopática/etiologia , Púrpura Trombocitopênica Idiopática/metabolismo , Púrpura Trombocitopênica Idiopática/patologia , Células Th1/metabolismo
15.
Parasitol Int ; 72: 101928, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31108221

RESUMO

The successful control and eradication of leishmaniasis are still challenging in view of the lack of adequate chemotherapy and potential prophylaxis. Research is going on for finding an appropriate anti-leishmanial drug which should be acceptable in terms of cost and safety. In view of this, the current study investigated the anti-leishmanial efficacy of salidroside (SAL) which is a phenylpropanoid glycoside. The leishmanicidal capacity of SAL was verified in vitro as well as in vivo. The SAL exhibited leishmanicidal activity against the promastigotes of L. donovani which was further validated by propidium iodide staining and its ability to arrest the promastigotes at the sub G0/G1 stage. SAL decreased and controlled the VL infection in mice as estimated by real-time PCR. Active immunomodulation was exhibited upon SAL treatment in BALB/c mice. The characteristic features like pronounced DTH reaction, polarization of immune status to Th1 type of immune response, increased the production of CD4+ and CD8+ T cells indicated the immune-stimulatory property of SAL. In addition to this the expression of NF-ĸB, iNOS genes along with the levels of leishmanicidal species, NO and ROS were found to be augmented in SAL treated infected animals. Moreover, SAL exhibited minimal toxicity to the THP-1 cells and it revealed no toxicity against liver and kidney. The capability of SAL in promoting the immune status in favor of host during VL infection without causing any side-effects may be used as an effective strategy to fight the disease.


Assuntos
Antiprotozoários/farmacologia , Glucosídeos/farmacologia , Leishmania donovani/efeitos dos fármacos , Fenóis/farmacologia , Animais , Linfócitos T CD8-Positivos/imunologia , Citocinas/imunologia , Humanos , Imunomodulação , Leishmaniose Visceral/tratamento farmacológico , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Subunidade p50 de NF-kappa B/genética , Óxido Nítrico Sintase Tipo II/genética , Baço/imunologia , Baço/parasitologia , Células THP-1 , Células Th1/imunologia
16.
Chirurgia (Bucur) ; 114(2): 152-161, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31060646

RESUMO

In the fine balance between tumor invasion and our defensive systems, the role played by the adaptive immune response at the tumor site is critical. Beyond the fact that all the immune components of the innate and adaptive response can be observed to varying degrees in the tumor microenvironment, it appears that a high density of T cytotoxic and memory lymphocytes, in a context of Th1 immune orientation in the tumor and its invasion front, provides a prognostic marker of paramount importance for colorectal cancer and more generally all solid tumors. The understanding of the role of immunity in cancer, tailored during one century of intensive research, has led to a complete paradigm shift.based on a sharp dissection In order to show the major impact of this conceptual revolution, we herein retrace through the example of colorectal cancer, how an effective immune test, namely the "Immunoscore", has been developed. We also provide up to date data demonstrating the capacity of the Immunoscore to prognosticate with a better accuracy than the TME classification clinical outcomes and to guide therapeutic strategies.


Assuntos
Neoplasias do Colo/imunologia , Indicadores Básicos de Saúde , Neoplasias Retais/imunologia , Microambiente Tumoral/imunologia , Imunidade Adaptativa/imunologia , Humanos , Prognóstico , Células Th1/imunologia , Resultado do Tratamento
17.
Appl Microbiol Biotechnol ; 103(12): 4977-4986, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31037380

RESUMO

Dengue virus (DENV) and Japanese encephalitis virus (JEV) are closely related mosquito-borne flaviviruses. Together, they caused most arthropod-borne diseases in the world. Previously, we had demonstrated that both live attenuated and inactivated JE vaccines elicited cross-protection against DENV infection, and a DNA vaccine candidate expressing JEV prM-E protein (named pCAG-JME) could provide effective protection against JEV infection in mice. In this study, we examined whether the same pCAG-JME could elicit cross-protection against DENV infection. Our results showed that pCAG-JME indeed induced cross-reactive antibodies and cross-protection against four different serotypes of DENV in mice. Interestingly, pCAG-JME-immunized mice also generated both Th1 and Th2 responses when stimulated by all four different serotypes of DENV antigens. Moreover, cross-primed CD8+ T cell response was also detected following the stimulation of DENV proteins using intracellular cytokine staining. In addition, sera from pCAG-JME-immunized mice significantly reduced the mortality caused by DENV2 infection in severe combination immunodeficiency mouse. These results suggest that both JE and DENV cross-reactive antibodies and cross-primed T cells might play important roles in the cross-protection. The findings of this study also indicate a possibility of developing novel multivalent genetically engineered vaccines against both JEV and DENV.


Assuntos
Antígenos Virais/imunologia , Proteção Cruzada , Vacinas contra Dengue/imunologia , Dengue/prevenção & controle , Vírus da Encefalite Japonesa (Espécie)/imunologia , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Antígenos Virais/genética , Vacinas contra Dengue/genética , Vírus da Dengue/classificação , Vírus da Dengue/imunologia , Vírus da Encefalite Japonesa (Espécie)/genética , Feminino , Imunização , Imunização Passiva , Camundongos , Camundongos Endogâmicos BALB C , Sorogrupo , Imunodeficiência Combinada Severa , Células Th1/imunologia , Células Th2/imunologia , Vacinas de DNA/genética , Vacinas de DNA/imunologia , Proteínas do Envelope Viral/genética
18.
Medicine (Baltimore) ; 98(21): e15774, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31124967

RESUMO

BACKGROUND: Melanoma-associated antigen-A (MAGE-A) was recognized as high-expressed in many solid tumors including esophageal carcinoma (EC), nevertheless, was reported to be low/not-expressed in normal tissues. Thus, it was considered as an extraordinary appropriate target for treatment especially in immunotherapy. Therefore, it demanded more detail knowledge on the precise function of MAGE-A. METHODS: In this study, we used the data from the Cancer Genome Atlas dataset (TCGA-ESCA) to analyze the expression and survival for MAGE A3/4/11 (the subtype of MAGE-A) using the online tool of UALCAN. Furthermore, the high-throughput sequencing data of the patients with esophageal squamous-cell carcinoma (ESCC) from TCGA dataset were performed to analyze the correlation test, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of MAGE A3/4/9/11 using LinkeDomics (online tool) and ClueGO (inner software of Cytoscape). Finally, relative gene expressions of MAGE A3/4/9/11 were verified by quantitative real-time PCR (q-PCR) in the patients with EC. RESULTS: MAGE A3/4/11 was high-expressed in tissues of patients with ESCC, and there was no difference in survival time for patients between the high-expressed with the low/medium-expressed. The Go enrichment analysis showed that the 4 MAGE-A subtypes (MAGE-A3/4/9/11) were enriched in the regulation of the adaptive immune response, translational initiation, interleukin-4 production, response to type I interferon, and skin development, respectively. The KEGG results showed that they were enriched in T cell receptor signaling pathway (MAGE-A3), Th1 and Th2 differentiation, antigen processing and presentation (MAGE-A4), cytokine-cytokine receptor interaction (MAGE-A9), and chemokine signaling pathway (MAGE-A11). CONCLUSION: MAGE A3/4/9/11 was high-expressed in EC, and were enrolled in the regulation of immune response. They may consider as candidate immune target for EC treatment and provided the messages for further research in the function of MAGE-A.


Assuntos
Antígenos de Neoplasias/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Proteínas de Neoplasias/genética , Imunidade Adaptativa/genética , Idoso , Antígenos de Neoplasias/imunologia , Biologia Computacional , Neoplasias Esofágicas/imunologia , Neoplasias Esofágicas/mortalidade , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/mortalidade , Esôfago/imunologia , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/imunologia , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , Células Th1/imunologia , Células Th2/imunologia
19.
J Agric Food Chem ; 67(22): 6313-6323, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31070910

RESUMO

Gliadins are major allergens responsible for wheat allergies. Food processing is an effective strategy to reduce the allergenicity of gluten. In the present study, we determined the secondary and tertiary structures of gluten and gliadins treated by chemical, physical, and enzymatic means through FTIR, surface hydrophobicity, intrinsic fluorescence spectra, and UV absorption spectra. The results showed that the three treatments of phosphorylation and alcalase and papain hydrolyses significantly changed the conformational structures of gliadins, especially the secondary structure. Then, the potential allergenicity of the phosphorylated and alcalase and papain hydrolyzed gliadins were further characterized, and we observed a significant decrease in the allergenicity through the results of the index of spleen, serum total IgE, gliadin-specific IgE, histamine, and serum cytokine concentrations. An elevation of Th17 cells, the absence of Treg cells, and an imbalance in Treg/Th17 are associated with allergy. On the basis of the expression levels of related cytokines and key transcription factors, we also confirmed that phosphorylation and alcalase and papain hydrolysis could effectively reduce the allergenicity of gliadins by improving the imbalance of both Th1/Th2 and Treg/Th17 in the spleens of sensitized mice. This study suggested that the changes in conformational structure contribute to gliadin hyposensitization and that phosphorylation and alcalase and papain hydrolysis may be promising strategies for the production of wheat products with low allergenicity.


Assuntos
Gliadina/química , Gliadina/imunologia , Papaína/química , Subtilisinas/química , Hipersensibilidade a Trigo/imunologia , Alérgenos/química , Alérgenos/imunologia , Animais , Biocatálise , Histamina/imunologia , Humanos , Hidrólise , Imunoglobulina E/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Baço/imunologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Triticum/química , Triticum/imunologia
20.
mSphere ; 4(3)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043512

RESUMO

Campylobacter jejuni is among the most common causes of diarrheal disease worldwide and efforts to develop protective measures against the pathogen are ongoing. One of the few defined virulence factors targeted for vaccine development is the capsule polysaccharide (CPS). We have developed a capsule conjugate vaccine against C. jejuni strain 81-176 (CPS-CRM) that is immunogenic in mice and nonhuman primates (NHPs) but only moderately immunogenic in humans when delivered alone or with aluminum hydroxide. To enhance immunogenicity, two novel liposome-based adjuvant systems, the Army Liposome Formulation (ALF), containing synthetic monophosphoryl lipid A, and ALF plus QS-21 (ALFQ), were evaluated with CPS-CRM in this study. In mice, ALF and ALFQ induced similar amounts of CPS-specific IgG that was significantly higher than levels induced by CPS-CRM alone. Qualitative differences in antibody responses were observed where CPS-CRM alone induced Th2-biased IgG1, whereas ALF and ALFQ enhanced Th1-mediated anti-CPS IgG2b and IgG2c and generated functional bactericidal antibody titers. CPS-CRM + ALFQ was superior to vaccine alone or CPS-CRM + ALF in augmenting antigen-specific Th1, Th2, and Th17 cytokine responses and a significantly higher proportion of CD4+ IFN-γ+ IL-2+ TNF-α+ and CD4+ IL-4+ IL-10+ T cells. ALFQ also significantly enhanced anti-CPS responses in NHPs when delivered with CPS-CRM compared to alum- or ALF-adjuvanted groups and showed the highest protective efficacy against diarrhea following orogastric challenge with C. jejuni This study provides evidence that the ALF adjuvants may provide enhanced immunogenicity of this and other novel C. jejuni capsule conjugate vaccines in humans.IMPORTANCE Campylobacter jejuni is a leading cause of diarrheal disease worldwide, and currently no preventative interventions are available. C. jejuni is an invasive mucosal pathogen that has a variety of polysaccharide structures on its surface, including a capsule. In phase 1 studies, a C. jejuni capsule conjugate vaccine was safe but poorly immunogenic when delivered alone or with aluminum hydroxide. Here, we report enhanced immunogenicity of the conjugate vaccine delivered with liposome adjuvants containing monophosphoryl lipid A without or with QS-21, known as ALF and ALFQ, respectively, in preclinical studies. Both liposome adjuvants significantly enhanced immunity in mice and nonhuman primates and improved protective efficacy of the vaccine compared to alum in a nonhuman primate C. jejuni diarrhea model, providing promising evidence that these potent adjuvant formulations may enhance immunogenicity in upcoming human studies with this C. jejuni conjugate and other malaria and HIV vaccine platforms.


Assuntos
Vacinas Bacterianas/imunologia , Infecções por Campylobacter/prevenção & controle , Imunogenicidade da Vacina , Lipídeo A/análogos & derivados , Saponinas/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antibacterianos/sangue , Infecções por Campylobacter/imunologia , Campylobacter jejuni/imunologia , Citocinas/imunologia , Feminino , Humanos , Imunoglobulina G/imunologia , Lipídeo A/administração & dosagem , Lipossomos/administração & dosagem , Lipossomos/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Primatas , Células Th1/imunologia , Células Th2/imunologia , Vacinas Conjugadas/administração & dosagem
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