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1.
Fish Shellfish Immunol ; 92: 621-628, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31260736

RESUMO

Intestine in fish is a complex multifunctional organ, not only plays roles in digestion and absorption of nutrient, but also has critical role in immunity. The present study evaluated the effects of different levels of dietary sodium butyrate [Butirex® C4 (Butirex)] on intestinal immune-,antioxidant-and tight junction-related gene expression injuvenile rainbow trout(Oncorhynchusmykiss). 240 healthy rainbow trout were dispensed in 12 fiberglass tanks appointed to four treatments [0 (control), 1.5 (B1.5), 2.5 (B2.5) and 5 (B5)g Butirex per kg diet]. After a 45-day feeding trial, the fish fed with the Butirex-supplemented diets showed higher intestinal lysozyme (LYZ), complement(ACH50) and bactericidal activities; the elevations in ACH50 and bactericidal activities depended on Butirex levels (P < 0.05). The Butirex-supplemented groups, particularly the B2.5 group, had significantly higher LYZ gene expression compared to the control group (P < 0.05). Butirex at 2.5 and 5 g/kg levels led to significantly higher IL-1ß gene expression. B2.5 and B5 had significantly lower and higher TNF-α gene expression compared to the control group (P < 0.05). The B2.5 group had significantly higher TGF-B, and significantly lower IL-8 compared to the control group (P < 0.05). The B1.5 and B2.5 group had significantly higher IL-10 gene expression compared to the control group (P < 0.05). The B2.5 and B5 groups had significantly higher SOD gene expression compared to the other groups; the highest expression was related to the B2.5 group (P < 0.05). Dietary Butirex supplementation significantly up-regulated CAT and GPx genes expression compared to the control group; the highest expression as related to the B2.5 and B5 groups (P < 0.05). The B2.5 group had significantly lower CLD12 gene expression compared to the control group (P < 0.05). The B2.5 and B5 groups had significantly higher CLD3, OCLD and ZO-1 gene expression compared to the control. The highest CLD3, ZO-1 gene expressions was related to the B2.5, and B5 groups respectively (P < 0.05). After challenge with Streptococcus iniae, B2.5 and B5 had significantly higher survival compared to the control group (55.6 ±â€¯7.70 and 68.9 ±â€¯10.2 vs. 33.3 ±â€¯6.67). In conclusion, Butirex is efficient immune stimulant and health booster in rainbow trout, which augments the fish resistance to disease. Modulation of immune components, cytokines, antioxidant system and intestinal integrity might involve in improving disease resistance in Butirex-treated fish. Although most of the examined genes were modulated by 2.5 g/kg Butirex under normal conditions, 5 g/kg level is recommended under pathogenic state to mitigate mortality.


Assuntos
Ácido Butírico/metabolismo , Resistência à Doença/efeitos dos fármacos , Doenças dos Peixes/imunologia , Imunidade Inata/efeitos dos fármacos , Oncorhynchus mykiss/imunologia , Transcriptoma/efeitos dos fármacos , Ração Animal/análise , Animais , Antioxidantes/metabolismo , Ácido Butírico/administração & dosagem , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Proteínas de Peixes/metabolismo , Intestinos/efeitos dos fármacos , Oncorhynchus mykiss/metabolismo , Distribuição Aleatória , Sódio na Dieta/administração & dosagem , Infecções Estreptocócicas/imunologia , Streptococcus iniae/fisiologia , Proteínas de Junções Íntimas/metabolismo , Transcriptoma/imunologia
2.
Fish Shellfish Immunol ; 92: 861-870, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31276791

RESUMO

Kuruma shrimp, a major farmed shrimp species in the world, includes two cryptic or sibling species, Form I (Marsupenaeus japonicus) and Form II (Marsupenaeus pulchricaudatus). Due to the lack of genomic resources, little is known about the molecular mechanisms associated with immune defense and hypoxia tolerance. Here, we sequenced the transcriptomes of two closely related Marsupenaeus species and compared genomic divergence. This study obtained 77049 and 84561 unigenes with N50 values of 1281bp and 1244bp for M. japonicus and M. pulchricaudatus, respectively, and 5036 pairs of putative orthologs were identified between two Marsupenaeus species. Estimation of Ka/Ks ratios indicated that 165 orthologous genes may be under positive selection (Ka/Ks > 0.5), including 49 pairs with a Ka/Ks ratio >1. According to the peak of synonymous rates, the divergence time between M. japonicus and M. pulchricaudatus was about 0.26-0.69 Mya. These positively selected orthologous genes related to the immune process mainly comprised single VWC domain protein, legumain, ras-related C3 botulinum, caspase, C-type lectin and were enriched in functions related to immune (Toll-like receptor and PI3K-Akt signaling) and hypoxia signaling (HIF-1 signaling and VEGF signaling). In this study, dozens of caspase-like unigenes were screened from two Marsupenaeus transcriptomes. Among these, the PjCaspase orthologous gene was subjected to positive selection (Ka/Ks = 1.22), which had different secondary and three-dimensional structure prediction. Based on the single copy caspase gene, eight populations of Marsupenaeus species were divided into two phylogeographic lineages from the East and South China. We characterized the transcriptomes of the two Marsupenaeus species and obtained several key orthologs associated with immune defense and hypoxia tolerance, which provides new insights into the immunity and genetic divergence of the two varieties. Moreover, this study will facilitate further comparative genomic studies of the two varieties.


Assuntos
Adaptação Biológica/fisiologia , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Imunidade Inata/genética , Penaeidae/fisiologia , Transcriptoma/imunologia , Anaerobiose , Animais , Evolução Molecular , Penaeidae/genética , Penaeidae/imunologia
3.
Fish Shellfish Immunol ; 92: 765-771, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31288099

RESUMO

The sea cucumber Apostichopus japonicus is a flourishing aquaculture species in China. However, there are challenges for sea cucumber aquaculture, one of which is the high temperature in summer. In this study, we explored the transcriptome expression profiles with seasons (APR, JUN and JUL) in the muscle tissue of A. japonicus. The temperature of the natural coast was 13 °C, 21 °C and 25 °C respectively when sampling. Compared with APR group, changes of expression profiles were more significant in JUL group than that in JUN group. A total of 46 differential expressed genes (DEGs) involved in both innate and adaptive immunity were highlighted, including 27 up-regulated and 19 down-regulated genes. They were further grouped into 10 sub-classes: heat shock, coagulation cascades, antigen processing and presentation, inflammatory response, transporter activity, immunoglobulin, lectin C, cell adhesion, reactive oxygen species (ROS) scavenging, apoptosis and autophagy. The study will offer deep insights of the molecular mechanisms underlying the physiological responses to seasonal high temperature in A. japonicus. Particularly, knowledge about the immunological effects of seasonal temperature on the species is critical for the optimal management practices for both wild and aquaculture populations.


Assuntos
Temperatura Alta , Imunidade Inata/genética , Stichopus/imunologia , Transcriptoma/imunologia , Animais , Perfilação da Expressão Gênica , Estações do Ano , Stichopus/genética
4.
Fish Shellfish Immunol ; 90: 308-316, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059812

RESUMO

Japanese pufferfish (Takifugu rubripes) is one of the main marine aquatic fish species cultured in Asia due to its high nutritional value. In recent years, disease caused by Vibrio harveyi infections have led to serious mortality in Japanese pufferfish industry. To understand the complex molecular mechanisms between V. harveyi and Japanese pufferfish, we performed a transcriptome analysis of liver and spleen samples from Japanese pufferfish at 1 and 2 day post-infection. Between-group comparisons revealed 922 genes that were significantly differentially expressed. The altered genes emphasized the function in several immune related pathways including MAPK signaling pathway, JAK-STAT signaling pathway, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction and lysosomal pathway. The data generated in this study provided insight into the responses of Japanese pufferfish against V. harveyi at the transcriptome level, promoting our comprehensive understanding of immune responses for aquatic animal against V. harveyi.


Assuntos
Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Takifugu/genética , Takifugu/imunologia , Transcriptoma/imunologia , Vibrio/fisiologia , Animais , Proteínas de Peixes/metabolismo , Perfilação da Expressão Gênica/veterinária , Fígado/imunologia , Fígado/metabolismo , Distribuição Aleatória , Baço/imunologia , Baço/metabolismo , Takifugu/metabolismo , Vibrioses/imunologia , Vibrioses/veterinária
5.
Fish Shellfish Immunol ; 90: 385-394, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31075406

RESUMO

For pearl culture of bivalve Hyriopsis cumingii, implantation of the sabio may cause nucleus discharge and increased host death rates. We performed a transcriptome analysis of the pearl sac of H. cumingii for 30 days after mantle implantation; 293863 unigenes were obtained, and 27176 unigenes were identified using nr, nt, KO, Swiss-Prot, Pfam, GO, and KOG databases. We detected 4878 differentially expressed genes (DEGs) through pairwise comparisons. We speculated that the physical condition of the recipient mussels returned to normal in about one month; the period was divided into six vital phases (0, 2 h-6 h, 12 h-24 h, 48 h to 7 days, 14 days and 30 days) on the basis of the overall similarities in DEGs. We compared the DEGs between time points and identified key immune-related genes. Our findings provide information on the immunological reactions induced by implantation in pearl mussels.


Assuntos
Imunidade Inata/genética , Transcriptoma/imunologia , Unionidae/genética , Unionidae/imunologia , Aloenxertos , Animais , Perfilação da Expressão Gênica
6.
Fish Shellfish Immunol ; 90: 109-117, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31051240

RESUMO

The immune response after allograft or xenograft transplantation in the pearl oyster is a major factor that cause its nucleus rejection and death. To determine the mechanism underlying the immune response after allograft and xenograft transplantations in the pearl oyster Pinctada fucata martensii, we constructed two sets of transcriptomes of hemocytes at different times (6 and 12 h; 1, 3, 6, 12, and 30 d) after allograft and xenograft transplantations, in which the xenografted mantle tissue was from Pinctada maxima. The transcriptomic analysis reveals many genes are involved in the immune response to transplantation, such as transient receptor potential cation channel (TRP), calmodulin (CaM), DNA replication-related genes, and sugar and lipid metabolism-related genes. The expression of these identified genes was higher in the host pearl oyster transplanted with xenograft than that by allograft. The histological analysis of the pearl sac also confirmed that many hemocytes were still gathered around the transplanted nucleus, and no pearl sac was formed in the host pearl oysters at 30 d after xenograft transplantation. The genomic analysis indicated that pearl oysters evolved many copies of genes, such as TRP, CaM, and GST, to sense and cope with the immune response after transplantation. "Ribosome" and "Cytosolic DNA-sensing pathway" were specifically induced in the xenograft group, whereas "Notch signaling pathway" specifically responded to the allograft transplantation. These results can improve our understanding of the mechanism underlying the immune response of pearl oysters after allograft and xenograft transplantations.


Assuntos
Genoma/imunologia , Imunidade Inata/genética , Pinctada/genética , Pinctada/imunologia , Transcriptoma/imunologia , Aloenxertos/imunologia , Animais , Perfilação da Expressão Gênica , Hemócitos/imunologia , Xenoenxertos/imunologia , Transplante Heterólogo/veterinária , Transplante Homólogo/veterinária
7.
Fish Shellfish Immunol ; 90: 141-149, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31055020

RESUMO

Metamorphosis is a transformation process in larval development associated with changes in morphological and physiological features, including the immune system. The gastrointestinal tract harbors a plethora of bacteria, which might affect the digestion and absorption of nutrients, immunity, and gut-brain crosstalk in the host. In this study, we have performed metagenomic and transcriptomic analyses on the intestines of grouper at the pre-, mid- and post-metamorphosis stages. The sequencing data of 16S rRNA gene showed drastic changes in the microbial communities at different developmental stages. The transcriptomic data revealed that the leukocyte transendothelial migration and the phagosome pathways might play important roles in mediating immunity in grouper at the three developmental stages. This information will increase our understanding of the metamorphosis process in grouper larvae, and shed light on the development of antimicrobial strategy during larval development.


Assuntos
Bass/genética , Bass/microbiologia , Microbioma Gastrointestinal/fisiologia , Imunidade Inata/genética , Transcriptoma/imunologia , Animais , Bass/crescimento & desenvolvimento , Bass/imunologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia , Metagenômica , Metamorfose Biológica/genética , Metamorfose Biológica/imunologia
8.
Fish Shellfish Immunol ; 89: 337-344, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30974216

RESUMO

Grass carp shares the largest portion of the aquaculture production in China, but hemorrhagic disease caused by grass carp reovirus (GCRV) often results in tremendous loss of fingerlings and yearlings, causing significant economic damages. However, it is difficult to study antiviral mechanisms in grass carp in vivo due to its large size and long reproductive cycle. Therefore, a small cyprinid species named rare minnow with high sensitivity to GCRV, is regarded as a useful model to study the mechanisms of this disease. In this study, rare minnows were infected with the type-IIGCRV (GCRV-HZ08), and pathogenesis was investigated by BGISEQ-500 transcriptome sequencing of four cDNA libraries, hepatopancreas, gills, head-kidney and spleen, and real time quantitative PCR (qRT-PCR). We obtained 51.22 Gb bases in total, and de novo assembled 107,756 unigenes with an average length of 1,441 bp. GO analysis revealed that the differentially expressed genes (DEGs) involved in the defense mechanisms were the most enriched GO terms in all four tissues. KEGG analysis revealed that the most enriched pathways were "Influenza A", "Herpes simplex infection", "Transcriptional misregulation in cancer" and "Metabolic" pathways. We also performed a comparative transcriptomic study between GCRV-infected rare minnow and grass carp data. This revealed that "IL-17 signaling pathway", "NF-kappa B signaling pathway" and "Influenza A" pathways are conserved (important) in the regulation of anti-GCRV infection in both species, and need to be further investigated. Furthermore, a total of four immune-related DEGs were selected for qRT-PCR validation, and the results confirmed the RNA-seq data. These results enhance our understanding of the antiviral responses of cyprinid fish infected by GCRV.


Assuntos
Cyprinidae/genética , Cyprinidae/imunologia , Doenças dos Peixes/imunologia , Transcriptoma/imunologia , Animais , Perfilação da Expressão Gênica/veterinária , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Reoviridae/fisiologia , Infecções por Reoviridae/imunologia , Infecções por Reoviridae/veterinária
9.
Fish Shellfish Immunol ; 91: 369-375, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30999042

RESUMO

Comparative transcriptome analysis via high throughput sequencing was applied to gain knowledge on the immune response in Litopenaeus vannamei reared in biofloc technology systems (BFT). Two types of carbon sources, namely, traditional carbon sources (molasses) and biodegradable polymers [hydroxybutyric acid-co-3-hydroxyvaleric acid (PHBV)] were used in BFT systems. Clear water systems without the addition of carbon sources were treated as the control. Water quality assays showed that the average concentrations of several stress factors, including nitrite, nitrate and TSS, were the highest in molasses-based BFT systems. After sequencing and comparing the transcriptome profiles of the L. vannamei hepatopancreas, 743 and 201 genes were significantly differentially expressed in molasses- and PHBV-based BFT systems, respectively. GO enrichment analysis, which was performed using the differentially expressed genes, revealed seven significantly over-represented GO terms in molasses-based BFT systems, including catabolic process, hydrolase activity, cellular localization, organic substance metabolic process, cellular metabolic process, establishment of localization and response to stress. The captured key genes were mainly involved in the pathways including cellular stress response, immune response and pathogen recognition. However, no GO terms were significantly over-represented in PHBV-based BFT systems compared with control. This study indicates that shrimp are subject to stress in BFT systems when molasses serves as the carbon source. Thus, PHBV may be a better alternative.


Assuntos
Hepatopâncreas/imunologia , Penaeidae/imunologia , Estresse Fisiológico/imunologia , Transcriptoma/imunologia , Animais , Aquicultura , Sequenciamento de Nucleotídeos em Larga Escala , Melaço , Penaeidae/genética , Poliésteres/metabolismo , Qualidade da Água
10.
Nat Commun ; 10(1): 1671, 2019 04 11.
Artigo em Inglês | MEDLINE | ID: mdl-30975994

RESUMO

Host and environmental factors contribute to variation in human immune responses, yet the genetic and evolutionary drivers of alternative splicing in response to infection remain largely uncharacterised. Leveraging 970 RNA-sequencing profiles of resting and stimulated monocytes from 200 individuals of African- and European-descent, we show that immune activation elicits a marked remodelling of the isoform repertoire, while increasing the levels of erroneous splicing. We identify 1,464 loci associated with variation in isoform usage (sQTLs), 9% of them being stimulation-specific, which are enriched in disease-related loci. Furthermore, we detect a longstanding increased plasticity of immune gene splicing, and show that positive selection and Neanderthal introgression have both contributed to diversify the splicing landscape of human populations. Together, these findings suggest that differential isoform usage has been an important substrate of innovation in the long-term evolution of immune responses and a more recent vehicle of population local adaptation.


Assuntos
Processamento Alternativo/imunologia , Imunidade/genética , Infecção/imunologia , Seleção Genética/imunologia , Transcriptoma/imunologia , Grupo com Ancestrais do Continente Africano/genética , Animais , Evolução Biológica , Grupo com Ancestrais do Continente Europeu/genética , Variação Genética/imunologia , Voluntários Saudáveis , Humanos , Masculino , Homem de Neandertal/genética , Polimorfismo de Nucleotídeo Único , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Locos de Características Quantitativas/imunologia , Análise de Sequência de RNA , Sequenciamento Completo do Exoma
11.
Nat Commun ; 10(1): 1914, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015473

RESUMO

Degradation of extracellular matrix (ECM) underlies loss of cartilage tissue in osteoarthritis, a common disease for which no effective disease-modifying therapy currently exists. Here we describe BNTA, a small molecule with ECM modulatory properties. BNTA promotes generation of ECM components in cultured chondrocytes isolated from individuals with osteoarthritis. In human osteoarthritic cartilage explants, BNTA treatment stimulates expression of ECM components while suppressing inflammatory mediators. Intra-articular injection of BNTA delays the disease progression in a trauma-induced rat model of osteoarthritis. Furthermore, we identify superoxide dismutase 3 (SOD3) as a mediator of BNTA activity. BNTA induces SOD3 expression and superoxide anion elimination in osteoarthritic chondrocyte culture, and ectopic SOD3 expression recapitulates the effect of BNTA on ECM biosynthesis. These observations identify SOD3 as a relevant drug target, and BNTA as a potential therapeutic agent in osteoarthritis.


Assuntos
Anti-Inflamatórios/farmacologia , Benzamidas/farmacologia , Cartilagem Articular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Depuradores de Radicais Livres/farmacologia , Fatores Imunológicos/farmacologia , Osteoartrite/tratamento farmacológico , Sulfonamidas/farmacologia , Animais , Cartilagem Articular/imunologia , Cartilagem Articular/patologia , Condrócitos/efeitos dos fármacos , Condrócitos/imunologia , Condrócitos/patologia , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Progressão da Doença , Matriz Extracelular/imunologia , Matriz Extracelular/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Injeções Intra-Articulares , Masculino , Osteoartrite/genética , Osteoartrite/imunologia , Osteoartrite/patologia , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/genética , Superóxido Dismutase/imunologia , Superóxidos/antagonistas & inibidores , Superóxidos/metabolismo , Transcriptoma/imunologia
12.
Nat Immunol ; 20(5): 637-651, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30962590

RESUMO

Respiratory infections are common precursors to asthma exacerbations in children, but molecular immune responses that determine whether and how an infection causes an exacerbation are poorly understood. By using systems-scale network analysis, we identify repertoires of cellular transcriptional pathways that lead to and underlie distinct patterns of asthma exacerbation. Specifically, in both virus-associated and nonviral exacerbations, we demonstrate a set of core exacerbation modules, among which epithelial-associated SMAD3 signaling is upregulated and lymphocyte response pathways are downregulated early in exacerbation, followed by later upregulation of effector pathways including epidermal growth factor receptor signaling, extracellular matrix production, mucus hypersecretion, and eosinophil activation. We show an additional set of multiple inflammatory cell pathways involved in virus-associated exacerbations, in contrast to squamous cell pathways associated with nonviral exacerbations. Our work introduces an in vivo molecular platform to investigate, in a clinical setting, both the mechanisms of disease pathogenesis and therapeutic targets to modify exacerbations.


Assuntos
Asma/imunologia , Redes Reguladoras de Genes/imunologia , Transcriptoma/imunologia , Viroses/imunologia , Adolescente , Asma/genética , Asma/virologia , Estudos de Casos e Controles , Criança , Resfriado Comum/genética , Resfriado Comum/imunologia , Resfriado Comum/virologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Estudos Prospectivos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Viroses/genética , Viroses/virologia
13.
Cancer Immunol Immunother ; 68(6): 937-949, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30953118

RESUMO

Gliomas appear to be highly immunosuppressive tumors, with a strong myeloid component. This includes MDSCs, which are a heterogeneous, immature myeloid cell population expressing myeloid markers Siglec-3 (CD33) and CD11b and lacking markers of mature myeloid cells including MHC II. Siglec-3 is a member of the sialic acid-binding immunoglobulin-like lectin (Siglec) family and has been suggested to promote MDSC expansion and suppression. Siglecs form a recently defined family of receptors with potential immunoregulatory functions but only limited insight in their expression on immune regulatory cell subsets, prompting us to investigate Siglec expression on MDSCs. We determined the expression of different Siglec family members on monocytic-MDSCs (M-MDSCs) and polymorphnuclear-MDSCs (PMN-MDSCs) from blood of glioma patients and healthy donors, as well as from patient-derived tumor material. Furthermore, we investigated the presence of sialic acid ligands for these Siglecs on MDSCs and in the glioma tumor microenvironment. Both MDSC subsets express Siglec-3, -5, -7 and -9, with higher levels of Siglec-3, -7 and -9 on M-MDSCs and higher Siglec-5 levels on PMN-MDSCs. Similar Siglec expression profiles were found on MDSCs from healthy donors. Furthermore, the presence of Siglec-5 and -9 was also confirmed on PMN-MDSCs from glioma tissue. Interestingly, freshly isolated glioma cells predominantly expressed sialic acid ligands for Siglec-7 and -9, which was confirmed in situ. In conclusion, our data show a distinct Siglec expression profile for M- and PMN-MDSCs and propose possible sialic acid-Siglec interactions between glioma cells and MDSCs in the tumor microenvironment.


Assuntos
Neoplasias Encefálicas/imunologia , Glioma/imunologia , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/imunologia , Transcriptoma/imunologia , Adulto , Idoso , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Linhagem Celular Tumoral , Feminino , Glioma/genética , Glioma/terapia , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , Isoformas de Proteínas/metabolismo , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/genética , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia
14.
Cancer Immunol Immunother ; 68(6): 973-982, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30963193

RESUMO

BACKGROUND: Pleomorphic dermal sarcomas (PDS) are sarcomas of the skin with local recurrences in up to 28% of cases, and distant metastases in up to 20%. Although recent evidence provides a strong rational to explore immunotherapeutics in solid tumors, nothing is known about the immune environment of PDS. METHODS: In the current study, a comprehensive immune-phenotyping of 14 PDS using RNA and protein expression analyses, as well as quantitative assessment of immune cells using an image-analysis tool was performed. RESULTS: Three out of 14 PDS revealed high levels of CD8-positive tumor-infiltrating T-lymphocytes (TILs), also showing elevated levels of immune-related cytokines such as IL1A, IL2, as well as markers that were very recently linked to enhanced response of immunotherapy in malignant melanoma, including CD27, and CD40L. Using a multivariate analysis, we found a number of differentially expressed genes in the CD8-high group including: CD74, LYZ and HLA-B, while the remaining cases revealed enhanced levels of immune-suppressive cytokines including CXCL14. The "CD8-high" PDS showed strong MHC-I expression and revealed infiltration by PD-L1-, PD-1- and LAG-3-expressing immune cells. Tumor-associated macrophages (TAMs) predominantly consisted of CD68 + , CD163 + , and CD204 + M2 macrophages showing an accentuation at the tumor invasion front. CONCLUSIONS: Together, we provide first explorative evidence about the immune-environment of PDS tumors that may guide future decisions whether individuals presenting with advanced PDS could qualify for immunotherapeutic options.


Assuntos
Imunofenotipagem/métodos , Sarcoma/imunologia , Neoplasias Cutâneas/imunologia , Transcriptoma/imunologia , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/genética , Antígeno B7-H1/imunologia , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Imunoterapia/métodos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/imunologia , Receptor de Morte Celular Programada 1/metabolismo , Sarcoma/genética , Sarcoma/terapia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia
15.
Fish Shellfish Immunol ; 89: 505-515, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30940577

RESUMO

The scallop Argopecten purpuratus is one of the most economically important cultured mollusks on the coasts from Chile and Peru but its production has declined, in part, due to the emergence of mass mortality events of unknown origin. Driven by this scenario, increasing progress has been made in recent years in the comprehension of immune response mechanisms in this species. However, it is still not entirely understood how different mucosal interfaces participate and cooperate with the immune competent cells, the hemocytes, in the immune defense. Thus, in this work we aimed to characterize the transcriptome of three tissues with immune relevance from A. purpuratus by next-generation sequencing and de novo transcriptome assembly. For this, 18 cDNA libraries were constructed from digestive gland, gills and hemocytes tissues of scallops from different immune conditions and sequenced by the Illumina HiSeq4000 platform. A total of 967.964.884 raw reads were obtained and 967.432.652 clean reads were generated. The clean reads were de novo assembled into 46.601 high quality contigs and 32.299 (69.31%) contigs were subsequently annotated. In addition, three de novo specific assemblies were performed from clean reads obtained from each tissue cDNA libraries for their comparison. Gene ontology (GO) and KEGG analyses revealed that annotated sequences from digestive gland, gills and hemocytes could be classified into both general and specific subcategory terms and known biological pathways, respectively, according to the tissue nature. Finally, several immune related candidate genes were identified, and the differential expression of tissue-specific genes was established, suggesting they could display specific roles in the host defense. The data presented in this study provide the first insight into the tissue specific transcriptome profiles of A. purpuratus, which should be considered for further research on the interplay between the hemocytes and mucosal immune responses.


Assuntos
Pectinidae/genética , Transcriptoma/imunologia , Animais , Perfilação da Expressão Gênica , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Pectinidae/imunologia
16.
Fish Shellfish Immunol ; 89: 710-718, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30999043

RESUMO

The horizontal transmission of lymphocystis disease virus (LCDV) through contaminated water and feed (using artemia as vehicle) and the associated immune gene expression profiles in Senegalese sole post-larvae were investigated. All specimens analyzed were positive for LCDV DNA detection at 1-day post-challenge (1 dpc) with the highest viral levels in specimens infected through the immersion route. However, the percentage of LCDV-positive animals and number of viral DNA copies dropped progressively at 2 and 7 dpc. The histological analysis identified structural changes in the skin, muscle and gills of sole post-larvae LCDV-challenged by immersion. In situ hybridization confirmed a wide distribution of LCDV in the skin, gut, surrounding vessels in trunk muscle and head kidney in the immersion route, while the signals were restricted to the liver and lamina propria in the feeding treatment. Expression analysis using a set of 22 genes related to innate immune defense system demonstrated clear differences in the time-course response to LCDV as function of the infection route. Most antiviral defense genes, the proinflammatory cytokines, the complement c3, g-type lysozyme and T-cell markers cd4 and cd8a were rapidly induced in the feeding-infected post-larvae, and they were remained activated at 2 dpc. In contrast, in the immersion-infected post-larvae the induction of most defensive genes was delayed, with a low intensity at 2 dpc. All these data demonstrate that LCDV can horizontally infect Senegalese sole post-larvae through the water or feed although with different patterns of histopathological disorders, virus distribution and route-specific expression profiles.


Assuntos
Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Linguados , Iridoviridae/fisiologia , Transcriptoma/imunologia , Carga Viral , Animais , Infecções por Vírus de DNA/imunologia , Infecções por Vírus de DNA/veterinária , Proteínas de Peixes/metabolismo , Distribuição Tecidual
17.
Nat Commun ; 10(1): 1607, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30962448

RESUMO

The outcome of fungal infections depends on interactions with innate immune cells. Within a population of macrophages encountering Candida albicans, there are distinct host-pathogen trajectories; however, little is known about the molecular heterogeneity that governs these fates. Here we developed an experimental system to separate interaction stages and single macrophage cells infected with C. albicans from uninfected cells and assessed transcriptional variability in the host and fungus. Macrophages displayed an initial up-regulation of pathways involved in phagocytosis and proinflammatory response after C. albicans exposure that declined during later time points. Phagocytosed C. albicans shifted expression programs to survive the nutrient poor phagosome and remodeled the cell wall. The transcriptomes of single infected macrophages and phagocytosed C. albicans displayed a tightly coordinated shift in gene expression co-stages and revealed expression bimodality and differential splicing that may drive infection outcome. This work establishes an approach for studying host-pathogen trajectories to resolve heterogeneity in dynamic populations.


Assuntos
Candida albicans/fisiologia , Regulação Fúngica da Expressão Gênica , Interações entre Hospedeiro e Microrganismos/genética , Macrófagos/imunologia , Fagocitose/imunologia , Animais , Separação Celular/métodos , Parede Celular/genética , Parede Celular/metabolismo , Células Cultivadas , Feminino , Citometria de Fluxo/métodos , Perfilação da Expressão Gênica , Interações entre Hospedeiro e Microrganismos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose/genética , Cultura Primária de Células , Processamento de RNA/imunologia , Transdução de Sinais/imunologia , Transcriptoma/imunologia
18.
Nat Commun ; 10(1): 1621, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30962454

RESUMO

The transcriptional regulator Rbpj is involved in T-helper (TH) subset polarization, but its function in Treg cells remains unclear. Here we show that Treg-specific Rbpj deletion leads to splenomegaly and lymphadenopathy despite increased numbers of Treg cells with a polyclonal TCR repertoire. A specific defect of Rbpj-deficient Treg cells in controlling TH2 polarization and B cell responses is observed, leading to the spontaneous formation of germinal centers and a TH2-associated immunoglobulin class switch. The observed phenotype is environment-dependent and can be induced by infection with parasitic nematodes. Rbpj-deficient Treg cells adopt open chromatin landscapes and gene expression profiles reminiscent of tissue-derived TH2-polarized Treg cells, with a prevailing signature of the transcription factor Gata-3. Taken together, our study suggests that Treg cells require Rbpj to specifically restrain TH2 responses, including their own excessive TH2-like differentiation potential.


Assuntos
Imunidade Celular , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Estrongiloidíase/imunologia , Linfócitos T Reguladores/imunologia , Células Th2/imunologia , Animais , Diferenciação Celular/imunologia , Modelos Animais de Doenças , Feminino , Fator de Transcrição GATA3/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia , Centro Germinativo/imunologia , Humanos , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/imunologia , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Strongyloides ratti/imunologia , Strongyloides ratti/patogenicidade , Estrongiloidíase/parasitologia , Linfócitos T Reguladores/metabolismo , Transcriptoma/imunologia
19.
Res Vet Sci ; 124: 166-177, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30903969

RESUMO

Sungri/96 vaccine strain is considered the most potent vaccine providing long-term immunity against peste des petits ruminants (PPR) in India. Previous studies in our laboratory highlighted induction of robust antiviral response in an interferon independent manner at 48 h and 120 h post infection (p.i.). However, immune response at the earliest time point 6 h p.i. (time taken to complete one PPRV life cycle), in PBMCs infected with Sungri/96 vaccine virus has not been investigated. This study was taken up to understand the global gene expression profiling of goat PBMCs after Sungri/96 PPRV vaccine strain infection at 6 h post infection (p.i.). A total of 1926 differentially expressed genes (DEGs) were identified with 616 - upregulated and 1310 - downregulated. TLR7/TLR3, IRF7/IRF1, ISG20, IFIT1/IFIT2, IFITM3, IL27 and TREX1 were identified as key immune sensors and antiviral candidate genes. Interestingly, type I interferons (IFNα/ß) were not differentially expressed at this time point as well. TREX1, an exonuclease which inhibits type I interferons at the early stage of virus infection was found to be highly upregulated. IL27, an important antiviral host immune factor was significantly upregulated. ISG20, an antiviral interferon induced gene with exonuclease activity specific to ssRNA viruses was highly expressed. Functional profiling of DEGs showed significant enrichment of immune system processes with 233 genes indicating initiation of immune defense response in host cells. Protein interaction network showed important innate immune molecules in the immune network with high connectivity. The study highlights important immune and antiviral genes at the earliest time point.


Assuntos
Doenças das Cabras/prevenção & controle , Imunidade Inata/genética , Leucócitos Mononucleares/imunologia , Peste dos Pequenos Ruminantes/imunologia , Transcriptoma/imunologia , Vacinas Virais/imunologia , Animais , Antivirais/imunologia , Perfilação da Expressão Gênica/veterinária , Doenças das Cabras/imunologia , Cabras , Índia , Interferons/imunologia , Leucócitos Mononucleares/virologia , Vírus da Peste dos Pequenos Ruminantes/imunologia
20.
Nat Commun ; 10(1): 1150, 2019 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-30850646

RESUMO

Frontal fibrosing alopecia (FFA) is a recently described inflammatory and scarring type of hair loss affecting almost exclusively women. Despite a dramatic recent increase in incidence the aetiopathogenesis of FFA remains unknown. We undertake genome-wide association studies in females from a UK cohort, comprising 844 cases and 3,760 controls, a Spanish cohort of 172 cases and 385 controls, and perform statistical meta-analysis. We observe genome-wide significant association with FFA at four genomic loci: 2p22.2, 6p21.1, 8q24.22 and 15q2.1. Within the 6p21.1 locus, fine-mapping indicates that the association is driven by the HLA-B*07:02 allele. At 2p22.1, we implicate a putative causal missense variant in CYP1B1, encoding the homonymous xenobiotic- and hormone-processing enzyme. Transcriptomic analysis of affected scalp tissue highlights overrepresentation of transcripts encoding components of innate and adaptive immune response pathways. These findings provide insight into disease pathogenesis and characterise FFA as a genetically predisposed immuno-inflammatory disorder driven by HLA-B*07:02.


Assuntos
Alopecia/congênito , Loci Gênicos , Predisposição Genética para Doença , Antígeno HLA-B7/genética , Transcriptoma/imunologia , Imunidade Adaptativa , Alopecia/diagnóstico , Alopecia/genética , Alopecia/fisiopatologia , Estudos de Casos e Controles , Estudos de Coortes , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/imunologia , Feminino , Expressão Gênica , Genoma Humano , Estudo de Associação Genômica Ampla , Antígeno HLA-B7/imunologia , Humanos , Imunidade Inata , Polimorfismo de Nucleotídeo Único
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