• 제목/요약/키워드: Antigen processing

검색결과 48건 처리시간 0.024초

Human Cytomegalovirus Inhibition of Interferon Signal Transduction

  • Miller, Daniel M.;Cebulla, Colleen M.;Sedmak, Daniel D.
    • Journal of Microbiology
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    • 제38권4호
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    • pp.203-208
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    • 2000
  • Cytomegalovirus (CMV), a beta-herpesvirus with worldwide distribution, exhibits host persistence, a distinguishing characteristic of all herpesviruses. This persistence is dependent upon restricted gene expression in infected cells as well as the ability of productively infected cells to escape from normal cell-mediated anti-viral immunosurveillance. Type I (IFN-$\alpha$/$\beta$) and type II (IFN-γ) interferons are major components of the innate defense system against viral infection. They are potent inducers of MHC class I and II antigens and of antigen processing proteins. Additionally, IFNS mediate direct antiviral effects through induction effector molecules that block viral infection and replications such as 2', 5-oligoadenylate synthetase (2, 5-OAS). IFNS function through activation of well-defined signal transduction pathways that involve phosphorylation of constituent proteins and ultimate formation of active transcription factors. Recent studies have shown that a number of diverse viruses, including CMV, EBV, HPV mumps and Ebola, are capable of inhibiting IFN-mediated signal transduction through a variety of mechanisms. As an example, CMV infection inhibits the ability of infected cells Is transcribe HLA class I and II antigens as well as the antiviral effector molecules 2, 5-OAS and MxA I. EMSA studies have shown that IFN-$\alpha$ and IFN-γ are unable to induce complete signal transduction in the presence of CMV infection, phenomena that are associated with specific decreases in JAKl and p48. Viral inhibition of IFN signal transduction represents a new mechanistic paradigm for increased viral survival, a paradigm predicting widespread consequences in the case of signal transduction factors common to multiple cytokine pathways.

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Differential Gene Expression Common to Acquired and Intrinsic Resistance to BRAF Inhibitor Revealed by RNA-Seq Analysis

  • Ahn, Jun-Ho;Hwang, Sung-Hee;Cho, Hyun-Soo;Lee, Michael
    • Biomolecules & Therapeutics
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    • 제27권3호
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    • pp.302-310
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    • 2019
  • Melanoma cells have been shown to respond to BRAF inhibitors; however, intrinsic and acquired resistance limits their clinical application. In this study, we performed RNA-Seq analysis with BRAF inhibitor-sensitive (A375P) and -resistant (A375P/Mdr with acquired resistance and SK-MEL-2 with intrinsic resistance) melanoma cell lines, to reveal the genes and pathways potentially involved in intrinsic and acquired resistance to BRAF inhibitors. A total of 546 differentially expressed genes (DEGs), including 239 up-regulated and 307 down-regulated genes, were identified in both intrinsic and acquired resistant cells. Gene ontology (GO) analysis revealed that the top 10 biological processes associated with these genes included angiogenesis, immune response, cell adhesion, antigen processing and presentation, extracellular matrix organization, osteoblast differentiation, collagen catabolic process, viral entry into host cell, cell migration, and positive regulation of protein kinase B signaling. In addition, using the PAN-THER GO classification system, we showed that the highest enriched GOs targeted by the 546 DEGs were responses to cellular processes (ontology: biological process), binding (ontology: molecular function), and cell subcellular localization (ontology: cellular component). Ingenuity pathway analysis (IPA) network analysis showed a network that was common to two BRAF inhibitorresistant cells. Taken together, the present study may provide a useful platform to further reveal biological processes associated with BRAF inhibitor resistance, and present areas for therapeutic tool development to overcome BRAF inhibitor resistance.

Identification of Differentially-Methylated Genes and Pathways in Patients with Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage

  • Kim, Bong Jun;Youn, Dong Hyuk;Chang, In Bok;Kang, Keunsoo;Jeon, Jin Pyeong
    • Journal of Korean Neurosurgical Society
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    • 제65권1호
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    • pp.4-12
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    • 2022
  • Objective : We reported the differentially methylated genes in patients with subarachnoid hemorrhage (SAH) using bioinformatics analyses to explore the biological characteristics of the development of delayed cerebral ischemia (DCI). Methods : DNA methylation profiles obtained from 40 SAH patients from an epigenome-wide association study were analyzed. Functional enrichment analysis, protein-protein interaction (PPI) network, and module analyses were carried out. Results : A total of 13 patients (32.5%) experienced DCI during the follow-up. In total, we categorized the genes into the two groups of hypermethylation (n=910) and hypomethylation (n=870). The hypermethylated genes referred to biological processes of organic cyclic compound biosynthesis, nucleobase-containing compound biosynthesis, heterocycle biosynthesis, aromatic compound biosynthesis and cellular nitrogen compound biosynthesis. The hypomethylated genes referred to biological processes of carbohydrate metabolism, the regulation of cell size, and the detection of a stimulus, and molecular functions of amylase activity, and hydrolase activity. Based on PPI network and module analysis, three hypermethylation modules were mainly associated with antigen-processing, Golgi-to-ER retrograde transport, and G alpha (i) signaling events, and two hypomethylation modules were associated with post-translational protein phosphorylation and the regulation of natural killer cell chemotaxis. VHL, KIF3A, KIFAP3, RACGAP1, and OPRM1 were identified as hub genes for hypermethylation, and ALB and IL5 as hub genes for hypomethylation. Conclusion : This study provided novel insights into DCI pathogenesis following SAH. Differently methylated hub genes can be useful biomarkers for the accurate DCI diagnosis.

Major histocompatibility complex genes exhibit a potential immunological role in mixed Eimeria-infected broiler cecum analyzed using RNA sequencing

  • Minjun Kim;Thisarani Kalhari Ediriweera;Eunjin Cho;Yoonji Chung;Prabuddha Manjula;Myunghwan Yu;John Kariuki Macharia;Seonju Nam;Jun Heon Lee
    • Animal Bioscience
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    • 제37권6호
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    • pp.993-1000
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    • 2024
  • Objective: This study was conducted to investigate the differential expression of the major histocompatibility complex (MHC) gene region in Eimeria-infected broiler. Methods: We profiled gene expression of Eimeria-infected and uninfected ceca of broilers sampled at 4, 7, and 21 days post-infection (dpi) using RNA sequencing. Differentially expressed genes (DEGs) between two sample groups were identified at each time point. DEGs located on chicken chromosome 16 were used for further analysis. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis was conducted for the functional annotation of DEGs. Results: Fourteen significant (false discovery rate <0.1) DEGs were identified at 4 and 7 dpi and categorized into three groups: MHC-Y class I genes, MHC-B region genes, and non-MHC genes. In Eimeria-infected broilers, MHC-Y class I genes were upregulated at 4 dpi but downregulated at 7 dpi. This result implies that MHC-Y class I genes initially activated an immune response, which was then suppressed by Eimeria. Of the MHC-B region genes, the DMB1 gene was upregulated, and TAP-related genes significantly implemented antigen processing for MHC class I at 4 dpi, which was supported by KEGG pathway analysis. Conclusion: This study is the first to investigate MHC gene responses to coccidia infection in chickens using RNA sequencing. MHC-B and MHC-Y genes showed their immune responses in reaction to Eimeria infection. These findings are valuable for understanding chicken MHC gene function.

Dietary corn resistant starch regulates intestinal morphology and barrier functions by activating the Notch signaling pathway of broilers

  • Zhang, Yingying;Liu, Yingsen;Li, Jiaolong;Xing, Tong;Jiang, Yun;Zhang, Lin;Gao, Feng
    • Asian-Australasian Journal of Animal Sciences
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    • 제33권12호
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    • pp.2008-2020
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    • 2020
  • Objective: This study was conducted to investigate the effects of dietary corn resistant starch (RS) on the intestinal morphology and barrier functions of broilers. Methods: A total of 320 one-day-old broilers were randomly allocated to 5 dietary treatments: one normal corn-soybean (NC) diet, one corn-soybean-based diet supplementation with 20% corn starch (CS), and 3 corn-soybean-based diets supplementation with 4%, 8%, and 12% corn resistant starch (RS) (identified as 4% RS, 8% RS, and 12% RS, respectively). Each group had eight replicates with eight broilers per replicate. After 21 days feeding, one bird with a body weight (BW) close to the average BW of their replicate was selected and slaughtered. The samples of duodenum, jejunum, ileum, caecum digesta, and blood were collected. Results: Birds fed 4% RS, 8% RS and 12% RS diets showed lower feed intake, BW gain, jejunal villus height (VH), duodenal crypt depth (CD), jejunal VH/CD ratio, duodenal goblet cell density as well as mucin1 mRNA expressions compared to the NC group, but showed higher concentrations of cecal acetic acid and butyric acid, percentage of jejunal proliferating cell nuclear antigen-positive cells and delta like canonical Notch ligand 4 (Dll4), and hes family bHLH transcription factor 1 mRNA expressions. However, there were no differences on the plasma diamine oxidase activity and D-lactic acid concentration among all groups. Conclusion: These findings suggested that RS could suppress intestinal morphology and barrier functions by activating Notch pathway and inhibiting the development of goblet cells, resulting in decreased mucins and tight junction mRNA expression.

Folic acid supplementation regulates key immunity-associated genes and pathways during the periparturient period in dairy cows

  • Khan, Muhammad Zahoor;Zhang, Zhichao;Liu, Lei;Wang, Di;Mi, Siyuan;Liu, Xueqin;Liu, Gang;Guo, Gang;Li, Xizhi;Wang, Yachun;Yu, Ying
    • Asian-Australasian Journal of Animal Sciences
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    • 제33권9호
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    • pp.1507-1519
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    • 2020
  • Objective: The current research was aimed to profile the transcriptomic picture of the peripheral blood lymphocytes (PBLs) associated with immunity in Chinese Holsteins supplemented orally with coated folic acid during the periparturient period. Methods: The total of 123 perinatal cows were selected for this study and divided into three groups; group A (n = 41, 240 mg/500 kg cow/d), group B (n = 40, 120 mg/500 kg cow/d) and group C (n = 42, 0 mg/cow/d) based on the quantity of folic acid fed. Three samples of PBLs were selected from each folic acid treated group (high, low, and control) and RNA sequencing method was carried out for transcriptomic analysis. Results: The analysis revealed that a higher number of genes and pathways were regulated in response to high and low folic acid supplementation compared to the controls. We reported the novel pathways tumor necrosis factor (TNF) signaling, antigen processing and presentation, Staphylococcus aureus infection and nuclear factor (NF)-kappa B signaling pathways) and the key genes (e.g. C-X-C motif chemokine ligand 10, TNF receptor superfamily member 1A, cluster difference 4, major histocompatibility complex, class II, DQ beta, NF-kappa-B inhibitor alpha, and TNF superfamily 13) having great importance in immunity and anti-inflammation in the periparturient cows in response to coated folic acid treatment. Conclusion: Collectively, our study profiled first-time transcriptomic analysis of bovine lymphocytes and compared the involved cytokines, genes, and pathways between high vs control and low vs control. Our data suggest that the low folic acid supplementation (120 mg/500 kg) could be a good choice to boost appropriate immunity and anti-inflammation as well as might being applied to the health improvement of perinatal dairy cows.

매독진단(梅毒診斷)을 위(爲)한 신속(迅速)한 혈장항체검사법(血漿抗體檢査法)에 관(關)한 연구(硏究) (Studies on the Rapid Plasma Reagin(RPR) Card Test for the Diagnosis of Syphilis)

  • 김주덕;유준;김현주
    • 대한미생물학회지
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    • 제3권1호
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    • pp.15-23
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    • 1968
  • For the effective control of Syphilis, many investigators have developed a more rapid, simple and economical screening serological test which is adequately sensitive and specific. To fulfill the requirements of a more rapid serologic test for syphlis, a substitute for the conventional serum specimen was needed since considerable time and labor are involved in the processing of blood to serum. Burdon suggested the use of plasma in the serologic tests for syphilis as a substitute for serum. He noticed that plasma was more sensitive than serum in the Kline and Kahn tests, and attributed this to the presence of more antibody-like substance, "reagin" in plasma than in serum. However, to make plasma sufficiently sensitive, it was necessary to inactivate plasma by heating at a temperature of $56^{\circ}C$ for about 30 minutes. Heating of plasma resulted in the precipitation of fibrinogen which made centrifugation necessary to obtain dear plasma. Since the chief disadvantage to the use of unheated plasma(or serum) was a reduction in sensitivity of results-which probably was due to a labile factor such as complement-Portnoy et al began to consider rapid chemical methods of inactivation of plasma(or serum). They experienced that choline chloirde was shown to be anticomplementary which suggested its use as an inactivating agent for unheated plasma(or serum). In 1959 Portnoy et al reported the Rapid Plasma Reagin(RPR) Test for syphilis which is a more rapid, economical and simple. But still this test has many disadvantages as a rapid performing, field and office procedure, because it requires the usual laboratory equipments such as centrifuge, rotating machine, microscope etc. To substitute these disadvantages of the RPR test, in 1962, Portnoy et al developed the Rapid Plasma Reagin(RPR) card test for syphilis, which has the following advantages: a) Simplicity and rapidity of performance, b) Requires no laboratory equipments, c) Stable antigen suspension, d) Adequate sensitivity and specificity. This RPR card test can be used as a rapidly performing and screening test in field investigation, outpatient clinics, small laboratories and hospitals doing limited syphilis serology, and predonor in blood bank. Private clinic which has limited laboratory equipment and technic for syphilis serology can also use this RPR card test as a tool in the rapid diagnosis of syphilis. It was thought that this RPR card test is a useful tool in Korea for private physician and mass survey for syphilis diagnosis. But Portnoy patented the reagents needed for the performing the RPR card test. Therefore authors developed newly the reagents and according to Portnoy's method evaluated the newly developed. RPR card test compared with the VDRL, Kolmer CF, and RPCF tests. The RPR card and VDRL tests were performed plasma and serum from the total 1,132 cases. Among these 1,131 cases, 521 were syphilis suspected laboratory specimens, and 611 were syphilis unsuspected healthy young men. After screening with these two tests, the RPR card and VDRL tests, reactive specimens to the above one or both tests were retested by the Kolmer CF and RPCF tests.

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Transcriptome profiling identifies immune response genes against porcine reproductive and respiratory syndrome virus and Haemophilus parasuis co-infection in the lungs of piglets

  • Zhang, Jing;Wang, Jing;Zhang, Xiong;Zhao, Chunping;Zhou, Sixuan;Du, Chunlin;Tan, Ya;Zhang, Yu;Shi, Kaizhi
    • Journal of Veterinary Science
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    • 제23권1호
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    • pp.2.1-2.18
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    • 2022
  • Background: Co-infections of the porcine reproductive and respiratory syndrome virus (PRRSV) and the Haemophilus parasuis (HPS) are severe in Chinese pigs, but the immune response genes against co-infected with 2 pathogens in the lungs have not been reported. Objectives: To understand the effect of PRRSV and/or HPS infection on the genes expression associated with lung immune function. Methods: The expression of the immune-related genes was analyzed using RNA-sequencing and bioinformatics. Differentially expressed genes (DEGs) were detected and identified by quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC) and western blotting assays. Results: All experimental pigs showed clinical symptoms and lung lesions. RNA-seq analysis showed that 922 DEGs in co-challenged pigs were more than in the HPS group (709 DEGs) and the PRRSV group (676 DEGs). Eleven DEGs validated by qRT-PCR were consistent with the RNA sequencing results. Eleven common Kyoto Encyclopedia of Genes and Genomes pathways related to infection and immune were found in single-infected and co-challenged pigs, including autophagy, cytokine-cytokine receptor interaction, and antigen processing and presentation, involving different DEGs. A model of immune response to infection with PRRSV and HPS was predicted among the DEGs in the co-challenged pigs. Dual oxidase 1 (DUOX1) and interleukin-21 (IL21) were detected by IHC and western blot and showed significant differences between the co-challenged pigs and the controls. Conclusions: These findings elucidated the transcriptome changes in the lungs after PRRSV and/or HPS infections, providing ideas for further study to inhibit ROS production and promote pulmonary fibrosis caused by co-challenging with PRRSV and HPS.