RESUMO
Domestic buffalo production plays an economically important role in the Brazilian Amazon, but they are susceptible to many diseases favored by the tropical climate and annually flooded habitats, including ocular diseases. In this context, it is important to select genotypes that maximize innate ocular immunity in Amazonian herds. We aimed to characterise, for the first time, gene expression profiles of the innate immune system in the conjunctival membrane of buffalo. Ocular conjunctival tissue samples were collected from 60 clinically healthy slaughtered animals in the northern Brazilian state of Amapá. The samples were histologically processed for classification into three groups according to the quantitative degree of lymphoid tissue associated with the conjunctiva (discrete, G1; slight, G2; and moderate, G3 presence of lymphoid tissue). RT-PCR was used to quantify gene expression of inflammatory cytokine (IL6, IL10, TNFA, IFNG), Toll-like receptor 4 (TLR4), and Defensin beta 110 (DEFB110), relative to the endogenous GAPDH gene. G1 animals presented low expression for IL6, IL10, TNFA, and DEFB110, while G2 exhibited high expression for IL6, IL10, IFNG, and TLR4. All G3 animals showed high expression for all tested genes. These results suggest a greater resistance to pathogenic microorganisms of buffalos in the G3 group, and the proportion of lymphoid tissue associated with the conjunctiva may be related to the immune resistance of individuals.(AU)
A produção de búfalos domésticos desempenha um papel economicamente importante na Amazônia brasileira, mas eles são suscetíveis a muitas doenças favorecidas pelo clima tropical e habitats inundados anualmente, incluindo doenças oculares. Nesse contexto, é importante selecionar genótipos que maximizem a imunidade ocular inata em rebanhos amazônicos. Objetivamos caracterizar, pela primeira vez, perfis de expressão gênica do sistema imune inato na membrana conjuntival de búfalos. Amostras de tecido conjuntival ocular foram coletadas de 60 animais clinicamente saudáveis abatidos no estado do Amapá, norte do Brasil. As amostras foram processadas histologicamente para classificação em três grupos de acordo com o grau quantitativo de tecido linfoide associado à conjuntiva (discreta, G1; leve, G2; e moderada, G3 presença de tecido linfoide). RT-PCR foi utilizado para quantificar a expressão gênica de citocinas inflamatórias (IL6, IL10, TNFA, IFNG), receptor Toll-like 4 (TLR4) e Defensina beta 110 (DEFB110), em relação ao gene GAPDH endógeno. Os animais do G1 apresentaram baixa expressão para IL6, IL10, TNFA e DEFB110, enquanto G2 exibiu alta expressão para IL6, IL10, IFNG e TLR4. Todos os animais do G3 apresentaram alta expressão para todos os genes testados. Esses resultados sugerem maior resistência aos microrganismos patogênicos dos búfalos do grupo G3, e a proporção de tecido linfoide associado à conjuntiva pode estar relacionada à resistência imunológica dos indivíduos.(AU)
Assuntos
Búfalos/fisiologia , Expressão Gênica/imunologia , Biópsia/veterinária , Brasil , CitocinasRESUMO
BACKGROUND: Colorectal cancer is one of the most common malignancies. With continuous exploration of the interaction between tumor cells and the immune system, tumor immunotherapy has become a revolution. However, CRC remains one of the less effective tumors for immunotherapy. The tumor microenvironment plays an important role in tumorigenesis and progression. The aim of this study is to explore tumor microenvironment-related genes that can predict the prognosis of colorectal adenocarcinoma, and also to provide new ideas for the mechanism of tumor development as well as immunotherapy. METHODS: After estimating Stromalscore and Immunescore of colorectal adenocarcinoma tumor samples according to RNA-Seq expression data downloaded from TCGA, we screened for TME-related differential genes. We filtered prognosis-related core genes by constructing protein-protein interaction networks and making one-factor cox analysis for prognosis. Finally, the relative content of 22 immune cells in tumor tissues was evaluated, and then immune cells associated with core genes were identified. RESULTS: We screened 773 differential genes related to the TME. Then we identified C3 as a core gene associated with prognosis. Single gene analysis showed that C3 expression was significantly higher in tumor tissues than in normal tissues (p < 0.001). High C3 expression was associated with lower overall survival (p = 0.046). Tumor immune cell analysis showed that mast cells resting, mast cells activated, T cells CD4 memory activated, eosinophils, and macrophages M0 were C3-associated immune cells. CONCLUSIONS: C3 has potential as a biomarker for colorectal adenocarcinoma and could provide new research ideas for the diagnosis and treatment of colorectal adenocarcinoma, especially for immunotherapy.
Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Complemento C3/genética , Microambiente Tumoral/genética , Adenocarcinoma/imunologia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Bases de Dados Genéticas , Feminino , Expressão Gênica/imunologia , Humanos , Imunidade Celular , Imunoterapia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Mapas de Interação de Proteínas , Análise de Sequência de RNA , Estatísticas não Paramétricas , Microambiente Tumoral/imunologiaRESUMO
Introduction: Sepsis has pro- and anti-inflammatory processes caused by infectious agents. Sepsis survivors have impaired immune response due to immunosuppression. Gene expression during the inflammatory process is guided by transcriptional access to chromatin, with post-translational changes made in histones that determine whether the loci of the inflammatory gene are active, balanced, or suppressed. For this, a review literature was performed in PubMed included 'sepsis' and 'epigenetic' and 'immunosuppression' terms until May 2020.Areas covered: This review article explores the relationship between epigenetic mechanisms and the pathophysiology of sepsis. Epigenetic changes, vulnerable gene expression, and immunosuppression are related to inflammatory insults that can modify the dynamics of the central nervous system. Therefore, it is important to investigate the timing of these changes and their dynamics during the disease progression.Expert opinion: Epigenetic changes are associated with the main stages of sepsis, from the pathogen-host interaction to inflammation and immunosuppression. These changes are key regulators of gene expression during physiological and pathological conditions. Thus, epigenetic markers have significant prognostic and diagnostic potential in sepsis, and epigenetic changes can be explored in combination with therapeutic strategies in experimental models of the disease.
Assuntos
Epigênese Genética , Tolerância Imunológica , Sepse , Epigênese Genética/genética , Epigênese Genética/imunologia , Expressão Gênica/genética , Expressão Gênica/imunologia , Histonas/genética , Histonas/imunologia , Humanos , Tolerância Imunológica/genética , Tolerância Imunológica/imunologia , Mitocôndrias/imunologia , Mitocôndrias/metabolismo , Sepse/genética , Sepse/imunologia , Sepse/fisiopatologiaRESUMO
PURPOSE: The tumor immune microenvironment (TIME) is now considered as an important factor during gastric cancer (GC) development. This study identified a novel immune-related risk model for predicting prognosis and assessing the immune status of GC patients. METHODS: Transcriptomic data were obtained from the TCGA database. The differential expressed immune-related genes (IRGs) were identified through the ImmPort portal. Enrichment analysis was performed to explore the potential molecular mechanism of these IRGs. By the Cox regression analysis, we constructed the immune prognostic model. Then, the association between the model and the immune microenvironment was estimated. The model was validated in the GSE84433 dataset. RESULTS: Totally, we identified 222 differentially expressed IRGs. These IRGs were closely correlated with immune response and immune signaling pathways. Through the Cox regression analysis, we developed the immune prognostic model based on the expression of seven IRGs (CXCL3, NOX4, PROC, FAM19A4, RNASE2, IGHD2-15, CGB5). Patients were stratified into two groups according to immune-related risk scores. Survival analysis indicated that the prognosis of high-risk patients was poorer than low-risk patients. Moreover, the immune-related risk score was an independent prognostic biomarker. More importantly, we found that the infiltration level of immunosuppressive cells and the expression of inhibitory immune checkpoints were higher in high-risk patients. The immune microenvironment tended to be a suppressive status in patients with high-risk scores. CONCLUSION: This study demonstrated that our model had predictive value for prognosis and the TIME in GC. It might be a robust tool to improve personalized patient management.
Assuntos
Imunidade/genética , Modelos Imunológicos , Neoplasias Gástricas/imunologia , Microambiente Tumoral/imunologia , Quimiocinas CXC/genética , Citocinas/genética , Bases de Dados Genéticas , Progressão da Doença , Nanismo Hipofisário/genética , Neurotoxina Derivada de Eosinófilo/genética , Expressão Gênica/imunologia , Humanos , Proteínas de Checkpoint Imunológico/metabolismo , Tolerância Imunológica/genética , NADPH Oxidase 4/genética , Células-Tronco Neoplásicas/imunologia , Prognóstico , Análise de Regressão , Fatores de Risco , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Transcriptoma , Microambiente Tumoral/genéticaRESUMO
Pemphigus foliaceus (PF) is an autoimmune blistering skin disease characterized by the presence of pathogenic autoantibodies against desmoglein 1, a component of intercellular desmosome junctions. PF occurs sporadically across the globe and is endemic in some Brazilian regions. Because PF is a B-cell-mediated disease, we aimed to study the impact of variants within genes encoding molecules involved in the different steps of B-cell development and antibody production on the susceptibility of endemic PF. We analysed 3,336 single nucleotide polymorphisms (SNPs) from 167 candidate genes genotyped with Illumina microarray in a cohort of 227 PF patients and 193 controls. After quality control and exclusion of non-informative and redundant SNPs, 607 variants in 149 genes remained in the logistic regression analysis, in which sex and ancestry were included as covariates. Our results revealed 10 SNPs within or nearby 11 genes that were associated with susceptibility to endemic PF (OR >1.56; p < 0.005): rs6657275*G (TGFB2); rs1818545*A (RAG1/RAG2/IFTAP);rs10781530*A (PAXX), rs10870140*G and rs10781522*A (TRAF2); rs535068*A (TNFRSF1B); rs324011*A (STAT6);rs6432018*C (YWHAQ); rs17149161*C (YWHAG); and rs2070729*C (IRF1). Interestingly, these SNPs have been previously associated with differential gene expression, mostly in peripheral blood, in publicly available databases. For the first time, we show that polymorphisms in genes involved in B-cell development and antibody production confer differential susceptibility to endemic PF, and therefore are candidates for possible functional studies to understand immunoglobulin gene rearrangement and its impact on diseases.
Assuntos
Formação de Anticorpos/genética , Formação de Anticorpos/imunologia , Linfócitos B/imunologia , Pênfigo/genética , Pênfigo/imunologia , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoanticorpos/genética , Autoanticorpos/imunologia , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Brasil , Estudos de Casos e Controles , Criança , Estudos de Coortes , Feminino , Expressão Gênica/genética , Expressão Gênica/imunologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/imunologia , Adulto JovemRESUMO
In-vitro fertilization is a routine livestock-breeding technique widely used around the world. Several studies have reported the interaction of bovine viral-diarrhea virus (BVDV) with gametes and in-vitro-produced (IVP) bovine embryos. Since, gene expression in BVDV-infected IVP bovine embryos is scarcely addressed. The aim of this work was to evaluate the differential expression of genes involved in immune and inflammatory response. Groups of 20-25 embryos on Day 6 (morula stage) were exposed (infected) or not (control) to an NCP-BVDV strain in SOF medium. After 24 h, embryos that reached expanded blastocyst stage were washed. Total RNA of each embryo group was extracted to determine the transcription levels of 9 specific transcripts related with antiviral and inflammatory response by SYBR Green real time quantitative (RT-qPCR). Culture media and an aliquot of the last embryos wash on Day 7 were analyzed by titration and virus isolation, respectively. A conventional PCR confirmed BVDV presence in IVP embryos. A significantly higher expression of interferon-α was observed in blastocysts exposed to NCP-BVDV compared to the controls (p < 0.05). In this study, the upregulation of INFα and TLR7 genes involved in inflammatory and immune response in BVDV-infected IVP bovine embryos is a new finding in this field. This differential expression suggest that embryonic cells could function in a manner like immune cells by recognizing and responding early to interaction with viral pathogens. These results provide new insights into the action of BVDV on the complex molecular pathways controlling bovine early embryonic development.
Assuntos
Doença das Mucosas por Vírus da Diarreia Viral Bovina , Bovinos , Vírus da Diarreia Viral Bovina/imunologia , Desenvolvimento Embrionário/imunologia , Expressão Gênica/imunologia , Interferon-alfa , Animais , Doença das Mucosas por Vírus da Diarreia Viral Bovina/embriologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/imunologia , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Bovinos/embriologia , Bovinos/imunologia , Vírus da Diarreia Viral Bovina/isolamento & purificação , Embrião de Mamíferos/imunologia , Embrião de Mamíferos/virologia , Feminino , Fertilização in vitro , Interferon-alfa/imunologia , Receptor 7 Toll-Like/imunologiaRESUMO
The bovine viral diarrhea virus (BVDV-1) is a pathogen with the capacity to modulate the interferon type I system. To further investigate the effects of BVDV-1 on the production of the immune response, the Madin-Darby bovine kidney cell line was infected with the cytopathic CH001 field isolate of BVDV-1, and the IFNbeta expression profiles were analyzed. The results showed that cpBVDV-1 was able to induce the production of IFNbeta in a way similar to polyinosinic-polycytidylic acid, but with less intensity. Interestingly, all cpBVDV-1 activities were blocked by pharmacological inhibitors of the IRF-1, IRF-7, and NF-κB signaling pathway, and the level of IFNbeta decreased at the level of transcript and protein. These results, together with in silico analyses showing the presence of several regulatory consensus target motifs, suggest that cpBVDV-1 regulates IFNbeta expression in bovines through the activation of several key transcription factors. Collectively, the results suggest that during cpBVDV-1 infection, cross talk is evident between various signaling pathways involved in transcriptional activation of IFNbeta in cattle.
Assuntos
Doença das Mucosas por Vírus da Diarreia Viral Bovina/genética , Vírus da Diarreia Viral Bovina Tipo 1/imunologia , Regulação da Expressão Gênica/genética , Expressão Gênica/genética , Fator Regulador 1 de Interferon/genética , Fator Regulador 7 de Interferon/genética , NF-kappa B/genética , Animais , Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Bovinos , Linhagem Celular , Células Epiteliais/imunologia , Células Epiteliais/virologia , Expressão Gênica/imunologia , Regulação da Expressão Gênica/imunologia , Fator Regulador 1 de Interferon/imunologia , Fator Regulador 7 de Interferon/imunologia , NF-kappa B/imunologia , Transdução de Sinais/genética , Transdução de Sinais/imunologiaRESUMO
The immunostimulatory potential of the marine yeast Yarrowia lipolytica (D1 and N6 strains) administered orally was evaluated in the white shrimp Litopenaeus vannamei. Yeasts and commercial glucans were mixed with a commercial feed to formulate diets with a 1.1% concentration of immunostimulants. The shrimp were fed daily for a period of 21 days. Weekly determinations were performed for immunological parameters in hemolymph, such as total hemocyte count (THC), lysozyme activity (LYZ), prophenoloxidase activity, antioxidant enzymatic activities (superoxide dismutase [SOD], catalase [CAT], and peroxidases), and bactericidal activity against Vibrio parahaemolyticus. Expression profiles of penaeidin (PEN), lysozyme (LYZ), and prophenoloxidase (proPO) immune genes were evaluated in hemocytes. In general, an increase in the immune parameters was observed in shrimp fed yeast diet compared to glucan and the control diets. Yarrowia lipolytica, especially strain N6, provided maximum immunostimulatory effects evidenced by the increase of immune parameters (THC, LYZ, SOD, CAT) and gene expression profile. In conclusion, this study demonstrated that Y. lipolytica had immunostimulatory effects and increased bactericidal activity in L. vannamei hemocytes against V. parahaemolyticus. These findings open the path for the potential application of Y. lipolytica-based immunostimulant for shrimp aquaculture.
Assuntos
Antioxidantes/metabolismo , Expressão Gênica/imunologia , Imunidade Humoral , Imunidade Inata , Penaeidae/imunologia , Yarrowia/química , Fermento Seco/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Imunidade Humoral/efeitos dos fármacos , Imunidade Inata/imunologia , Distribuição Aleatória , Fermento Seco/administração & dosagemRESUMO
Paracoccidioides species cause paracoccidioidomycosis (PCM), a systemic mycosis highly prevalent in Brazil. Therapy of PCM has some issues that make studies for new therapeutic and vaccine targets relevant, such as the P. brasiliensis 60-kDa-heat-shock protein (PbHsp60), an immunogenic antigen that induces protection in experimental mice infection. Here, we investigated the relative expression of mRNA for PbHsp60 in P. brasiliensis in the different morphotypes of P. brasiliensis and in morphological transition phases. In addition, antibodies to rPbHsp60 were produced and used to analyze the location of PbHsp60 in yeast and hyphae by electron microscopy. The analyses showed a substantial increase in the relative amounts of HSP60 mRNA in yeast when compared to mycelium and an intermediate expression in transitional forms. Regarding the cell location, immunoelectron microscopy analysis revealed that PbHsp60 is within the cell wall. These observations suggest that this protein may be involved in the maintenance of the cell wall integrity and the interaction with the host for colonization, infection and pathogenesis.
Assuntos
Chaperonina 60/imunologia , Paracoccidioides/imunologia , RNA Mensageiro/imunologia , Animais , Antígenos de Fungos/imunologia , Expressão Gênica/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Paracoccidioides/patogenicidade , Reação em Cadeia da PolimeraseRESUMO
DNA methylation as a process that regulates gene expression is crucial in immune cells biology. Global and gene specific methylation changes have been described in autoimmunity, especially in Systemic Lupus Erythematosus. These changes not only contribute to the understanding of the disease, but also some have been proposed as diagnostic or disease activity biomarkers. The present review compiles the most recent discoveries on this field on each type of immune cells, including specific changes in signalling pathways, genes of interest and its possible applications on diagnosis or treatment.