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  1. Elvert M, Sauerhering L, Maisner A
    J Infect Dis, 2020 05 11;221(Suppl 4):S395-S400.
    PMID: 31665348 DOI: 10.1093/infdis/jiz455
    During the Nipah virus (NiV) outbreak in Malaysia, pigs and humans were infected. While pigs generally developed severe respiratory disease due to effective virus replication and associated inflammation processes in porcine airways, respiratory symptoms in humans were rare and less severe. To elucidate the reasons for the species-specific differences in NiV airway infections, we compared the cytokine responses as a first reaction to NiV in primary porcine and human bronchial epithelial cells (PBEpC and HBEpC, respectively). In both cell types, NiV infection resulted in the expression of type III interferons (IFN-λ). Upon infection with similar virus doses, viral RNA load and IFN expression were substantially higher in HBEpC. Even if PBEpC expressed the same viral RNA amounts as NiV-infected HBEpC, the porcine cells showed reduced IFN- and IFN-dependent antiviral gene expression. Despite this inherently limited IFN response, the expression of proinflammatory cytokines (IL-6, IL-8) in NiV-infected PBEpC was not decreased. The downregulation of antiviral activity in the presence of a functional proinflammatory cytokine response might be one of the species-specific factors contributing to efficient virus replication and acute inflammation in the lungs of pigs infected with the Malaysian NiV strain.
    Matched MeSH terms: Gene Expression Regulation/immunology
  2. Low CF, Shamsudin MN, Abdullah M, Chee HY, Aliyu-Paiko M
    J Fish Dis, 2015 Jan;38(1):17-25.
    PMID: 24397626 DOI: 10.1111/jfd.12195
    The mechanisms through which brown-marbled grouper accomplishes resistance to infection, particularly against Vibrios, are not yet fully understood. In this study, brown-marbled grouper fingerlings were experimentally infected with Vibrio parahaemolyticus, to identify disease resistance grouper, and the serum proteome profiles were compared between resistant and susceptible candidates, via two-dimensional gel electrophoresis (2-DE). The results showed that putative parvalbumin beta-2 subunit I, alpha-2-macroglobulin, nattectin and immunoglobulin light chain proteins were among proteins that significantly overexpressed in the resistant fish as compared to the susceptible group of fish, whereas apolipoprotein E and immunoglobulin light chain proteins were observed to be differentially overexpressed in the susceptible fish. Further analysis by peptide sequencing revealed that the immunoglobulin light chain proteins identified in the resistant and susceptible groups differed in amino acid composition. Taken together, the results demonstrated for the first time that putative parvalbumin beta-2 subunit I, alpha-2-macroglobulin, nattectin and immunoglobulin light chain are among important proteins participating to effect disease resistance mechanism in fish and were overexpressed to function collectively to resist V. parahaemolyticus infection. Most of these molecules are mediators of immune response.
    Matched MeSH terms: Gene Expression Regulation/immunology*
  3. Low CF, Shamsudin MN, Chee HY, Aliyu-Paiko M, Idrus ES
    J Fish Dis, 2014 Aug;37(8):693-701.
    PMID: 24304156 DOI: 10.1111/jfd.12153
    The gram-negative bacterium, Vibrio alginolyticus, has frequently been identified as the pathogen responsible for the infectious disease called vibriosis. This disease is one of the major challenges facing brown-marbled grouper aquaculture, causing fish farmers globally to suffer substantial economic losses. The objective of this study was to investigate the proteins involved in the immune response of brown-marbled grouper fingerlings during their initial encounter with pathogenic organisms. To achieve this objective, a challenge experiment was performed, in which healthy brown-marbled grouper fingerlings were divided into two groups. Fish in the treated group were subjected to intraperitoneal injection with an infectious dose of V. alginolyticus suspended in phosphate-buffered saline (PBS), and those in the control group were injected with an equal volume of PBS. Blood samples were collected from a replicate number of fish from both groups at 4 h post-challenge and analysed for immune response-related serum proteins via two-dimensional gel electrophoresis. The results showed that 14 protein spots were altered between the treated and control groups; these protein spots were further analysed to determine the identity of each protein via MALDI-TOF/TOF. Among the altered proteins, three were clearly overexpressed in the treated group compared with the control; these were identified as putative apolipoprotein A-I, natural killer cell enhancement factor and lysozyme g. Based on these results, these three highly expressed proteins participate in immune response-related reactions during the initial exposure (4 h) of brown-marbled grouper fingerling to V. alginolyticus infection.
    Matched MeSH terms: Gene Expression Regulation/immunology
  4. Ravichandran G, Pasupuleti M, Arasu MV, Al-Dhabi NA, Arshad A, Arockiaraj J
    Fish Shellfish Immunol, 2020 Nov;106:332-340.
    PMID: 32758637 DOI: 10.1016/j.fsi.2020.07.068
    The occurrences of multiple drug-resistant strains have been relentlessly increasing in recent years. The aquaculture industry has encountered major disease outbreaks and crucially affected by this situation. The usage of non-specific chemicals and antibiotics expedites the stimulation of resistant strains. Triggering the natural defense mechanism would provide an effective and safest way of protecting the host system. Hence, we have investigated the innate immune function of serine/threonine-protein kinase (STPK) in Macrobrachium rosenbergii (Mr). The in-silico protein analysis resulted in the identification of cationic antimicrobial peptide, MrSL-19, with interesting properties from STPK of M. rosenbergii. Antimicrobial assay, FACS and SEM analysis demonstrated that the peptide potentially inhibits Staphylococcus aureus by interacting with its membrane. The toxic study on MrSL-19 demonstrated that the peptide is not toxic against HEK293 cells as well as human erythrocytes. This investigation showed the significant innate immune property of an efficient cationic antimicrobial peptide, MrSL-19 of STPK from M. rosenbergii.
    Matched MeSH terms: Gene Expression Regulation/immunology*
  5. Faiz NM, Cortes AL, Guy JS, Fletcher OJ, Cimino T, Gimeno IM
    Avian Pathol, 2017 Aug;46(4):376-385.
    PMID: 28151004 DOI: 10.1080/03079457.2017.1290214
    Marek's disease virus (MDV) is a herpesvirus that induces lymphoma and immunosuppression in chickens. MDV-induced immunosuppression (MDV-IS) is complex and can be divided into two phases: early-MDV-IS associated with cytolytic infection in the lymphoid organs in chickens lacking maternal antibodies against MDV (MAbs) and late-MDV-IS that appears later in the pathogenesis and occurs even in chickens bearing MAbs. We have recently developed a model to reproduce late-MDV-IS under laboratory conditions. This model evaluates late-MDV-IS indirectly by assessing the effect of MDV infection on the efficacy of infectious laryngotracheitis (ILT) vaccines against challenge with ILT virus. In the present study, we have used this model to investigate the role of two factors (MDV pathotype and host sex) on the development of late-MDV-IS. Five MDV strains representing three different pathotypes: virulent (vMDV; 617A, GA), very virulent (vvMDV; Md5), and very virulent plus (vv+MDV; 648A, 686), were evaluated. Only vv+ strains were able to induce late-MDV-IS. An immunosuppression rank (IS-rank) was established based on the ability of MDV to reduce the efficacy of chicken embryo origin vaccine (values go from 0 to 100, with 100 being the highest immunosuppressive ability). The IS-rank of the evaluated MDV strains ranged from 5.97 (GA) to 20.8 (617A) in the vMDV strains, 5.97 to 16.24 in the vvMDV strain Md5, and 39.08 to 68.2 in the vv+ strains 648A and 686. In this study both male and female chickens were equally susceptible to MDV-IS by vv+MDV 686. Our findings suggest that late-MDV-IS is a unique feature of vv+ strains.
    Matched MeSH terms: Gene Expression Regulation/immunology
  6. Vellasamy S, Tong CK, Azhar NA, Kodiappan R, Chan SC, Veerakumarasivam A, et al.
    Cytotherapy, 2016 10;18(10):1270-83.
    PMID: 27543068 DOI: 10.1016/j.jcyt.2016.06.017
    BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have been identified as pan-immunosuppressant in various in vitro and in vivo inflammatory models. Although the immunosuppressive activity of MSCs has been explored in various contexts, the precise molecular signaling pathways that govern inhibitory functions remain poorly elucidated.

    METHODS: By using a microarray-based global gene expression profiling system, this study aimed to decipher the underlying molecular pathways that may mediate the immunosuppressive activity of umbilical cord-derived MSCs (UC-MSCs) on activated T cells.

    RESULTS: In the presence of UC-MSCs, the proliferation of activated T cells was suppressed in a dose-depended manner by cell-to-cell contact mode via an active cell-cycle arrest at the G0/G1 phase of the cell cycle. The microarray analysis revealed that particularly, IFNG, CXCL9, IL2, IL2RA and CCND3 genes were down-regulated, whereas IL11, VSIG4, GFA1, TIMP3 and BBC3 genes were up-regulated by UC-MSCs. The dysregulated gene clusters associated with immune-response-related ontologies, namely, lymphocyte proliferation or activation, apoptosis and cell cycle, were further analyzed.

    CONCLUSIONS: Among the nine canonical pathways identified, three pathways (namely T-helper cell differentiation, cyclins and cell cycle regulation, and gap/tight junction signalling pathways) were highly enriched with these dysregulated genes. The pathways represent putative molecular pathways through which UC-MSCs elicit immunosuppressive activity toward activated T cells. This study provides a global snapshot of gene networks and pathways that contribute to the ability of UC-MSCs to suppress activated T cells.

    Matched MeSH terms: Gene Expression Regulation/immunology
  7. Irving AT, Zhang Q, Kong PS, Luko K, Rozario P, Wen M, et al.
    Cell Rep, 2020 11 03;33(5):108345.
    PMID: 33147460 DOI: 10.1016/j.celrep.2020.108345
    Bat cells and tissue have elevated basal expression levels of antiviral genes commonly associated with interferon alpha (IFNα) signaling. Here, we show Interferon Regulatory Factor 1 (IRF1), 3, and 7 levels are elevated in most bat tissues and that, basally, IRFs contribute to the expression of type I IFN ligands and high expression of interferon regulated genes (IRGs). CRISPR knockout (KO) of IRF 1/3/7 in cells reveals distinct subsets of genes affected by each IRF in an IFN-ligand signaling-dependent and largely independent manner. As the master regulators of innate immunity, the IRFs control the kinetics and maintenance of the IRG response and play essential roles in response to influenza A virus (IAV), herpes simplex virus 1 (HSV-1), Melaka virus/Pteropine orthoreovirus 3 Melaka (PRV3M), and Middle East respiratory syndrome-related coronavirus (MERS-CoV) infection. With its differential expression in bats compared to that in humans, this highlights a critical role for basal IRF expression in viral responses and potentially immune cell development in bats with relevance for IRF function in human biology.
    Matched MeSH terms: Gene Expression Regulation/immunology*
  8. Arockiaraj J, Vanaraja P, Easwvaran S, Singh A, Othman RY, Bhassu S
    Fish Shellfish Immunol, 2011 Dec;31(6):1259-67.
    PMID: 21945707 DOI: 10.1016/j.fsi.2011.09.008
    Apoptosis is genetically programmed cellular killing processes that execute unnecessary or infected cells. It plays an important role in embryogenesis, homeostasis, insect metamorphosis and immunity. Apoptosis inhibitor (MrIAP) was sequenced from the freshwater giant prawn Macrobrachium rosenbergii using Illumina Solexa Genome Analyzer Technique. MrIAP consisted of 1753 base pair nucleotides encoded 535 polypeptide with an estimated molecular mass of 60 kDa. MrIAP amino acid sequence contains IAP superfamily domain between 5 and 490. The deduced amino acid sequences of the MrIAP were aligned with the other IAP family members. The highest sequence similarity was observed in IAP-5 from ant Camponotus floridanus (67%) followed by IAP from body louse Pediculus humanus corporis (66%) and the lowest (62%) in IAP-5 isoform-5 from common chimpanzee Pan troglodytes and IAP-5 from Aedes aegypti. The IAP phylogenetic tree showed that MrIAP closely related to other arthropod blacklegged tick Ixodes scapularis, formed a sister group with IAP from a hemichordate acorn worm Saccoglossus kowalevskii and finally clustered together with IAPs from fish groups. The quantitative real time PCR analysis revealed that significantly (P < 0.05) highest expression was noticed in hepatopancreas and significantly (P < 0.05) lowest expression in pleopods. Based on the results of gene expression analysis, MrIAP mRNA transcription in M. rosenbergii challenged to infectious hypodermal and hematopoietic necrosis virus (IHHNV) was highly induced in hepatopancreas. The collective results of this study indicate that the MrIAP is an essential immune gene and influences the immune response against IHHNV infection in M. rosenbergii.
    Matched MeSH terms: Gene Expression Regulation/immunology*
  9. Soleimani AF, Zulkifli I, Hair-Bejo M, Omar AR, Raha AR
    Poult Sci, 2012 Feb;91(2):340-5.
    PMID: 22252346 DOI: 10.3382/ps.2011-01703
    Environmental stressors may influence chicken performance and susceptibility to pathogens, such as Salmonella enteritidis. This study was conducted to determine the effects of heat shock protein (Hsp)70 expression on resistance to Salmonella enteritidis infection in broiler chickens subjected to heat exposure. Chicks were divided into 3 feeding regimens: ad libitum feeding (control); 60% feed restriction on d 4, 5, and 6 (FR60); and 60% feed restriction on d 4, 5, and 6 plus 1,500 mg/kg of quercetin (FR60Q). On d 35, all of the chickens were individually inoculated with 1 mL of Salmonella enteritidis (1.5 × 10(8) cfu/bird) and exposed to an ambient temperature of 37 ± 1°C and 70% RH for 3 h/d. The FR60 and FR60Q chickens had significantly lower Salmonella enteritidis colonization and lower Hsp70 expression than that of the control chickens following the heat exposure period. The least colonization was observed in the FR60Q group (1.38 log(10) cfu/g in the spleen and 1.96 log(10) cfu/g in the cecal content) and the highest was in the control group (2.1 log(10) cfu/g in the spleen and 4.42 log(10) cfu/g in the cecal content). It appears that neonatal feed restriction can enhance resistance to Salmonella enteritidis colonization in heat-stressed broiler chicks, and the underlying mechanism could be associated with the lower expression of Hsp70.
    Matched MeSH terms: Gene Expression Regulation/immunology
  10. Rasoli M, Yeap SK, Tan SW, Roohani K, Kristeen-Teo YW, Alitheen NB, et al.
    BMC Vet Res, 2015;11:75.
    PMID: 25884204 DOI: 10.1186/s12917-015-0377-x
    Very virulent infectious bursal disease virus (vvIBDV) induces immunosuppression and inflammation in young birds, which subsequently leads to high mortality. In addition, infectious bursal disease (IBD) is one of the leading causes of vaccine failure on farms. Therefore, understanding the immunopathogenesis of IBDV in both the spleen and the bursae could help effective vaccine development. However, previous studies only profiled the differential expression of a limited number of cytokines, in either the spleen or the bursae of Fabricius of IBDV-infected chickens. Thus, this study aims to evaluate the in vitro and in vivo immunoregulatory effects of vvIBDV infection on macrophage-like cells, spleen and bursae of Fabricius.
    Matched MeSH terms: Gene Expression Regulation/immunology
  11. Chow SC
    Arch Immunol Ther Exp (Warsz), 2009 Jul-Aug;57(4):243-51.
    PMID: 19578811 DOI: 10.1007/s00005-009-0038-5
    Statins are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) and they are the most effective agents for lowering cholesterol in clinical practice for the treatment of cardiovascular diseases. However, it has become clear that statins also have pleiotropic immunomodulatory effects in addition to their lipid-lowering properties. As a result, much attention has been focused on their potential as therapeutic agents for the treatment of inflammatory autoimmune diseases. In this review the effect of statins on the expression and function of a variety of immune-relevant molecules will be discussed alongside the underlying mechanisms that contribute to the immunomodulatory effects of statins.
    Matched MeSH terms: Gene Expression Regulation/immunology
  12. Ibahim MJ, Yang Y, Crosbie JC, Stevenson A, Cann L, Paiva P, et al.
    Radiat Res, 2016 Jan;185(1):60-8.
    PMID: 26720800 DOI: 10.1667/RR14115.1
    Synchrotron microbeam radiation treatment (MRT) is a preclinical radiotherapy technique with considerable clinical promise, although some of the underlying radiobiology of MRT is still not well understood. In recently reported studies, it has been suggested that MRT elicits a different tumor immune profile compared to broad-beam treatment (BB). The aim of this study was to investigate the effects of synchrotron MRT and BB on eosinophil-associated gene pathways and eosinophil numbers within and around the tumor in the acute stage, 48 h postirradiation. Balb/C mice were inoculated with EMT6.5 mouse mammary tumors and irradiated with microbeam radiation (112 and 560 Gy) and broad-beam radiation (5 and 9 Gy) at equivalent doses determined from a previous in vitro study. After tumors were collected 24 and 48 h postirradiation, RNA was extracted and quantitative PCR performed to assess eosinophil-associated gene expression. Immunohistochemistry was performed to detect two known markers of eosinophils: eosinophil-associated ribonucleases (EARs) and eosinophil major basic protein (MBP). We identified five genes associated with eosinophil function and recruitment (Ear11, Ccl24, Ccl6, Ccl9 and Ccl11) and all of them, except Ccl11, were differentially regulated in synchrotron microbeam-irradiated tumors compared to broad-beam-irradiated tumors. However, immunohistochemical localization demonstrated no significant differences in the number of EAR- and MBP-positive eosinophils infiltrating the primary tumor after MRT compared to BB. In conclusion, our work demonstrates that the effects of MRT on eosinophil-related gene pathways are different from broad-beam radiation treatment at doses previously demonstrated to be equivalent in an in vitro study. However, a comparison of the microenvironments of tumors, which received MRT and BB, 48 h after exposure showed no difference between them with respect to eosinophil accumulation. These findings contribute to our understanding of the role of differential effects of MRT on the tumor immune response.
    Matched MeSH terms: Gene Expression Regulation/immunology
  13. Norazmi MN, Mohamed R, Nurul AA, Yaacob NS
    Clin. Dev. Immunol., 2012;2012:849195.
    PMID: 22548115 DOI: 10.1155/2012/849195
    Given their roles in immune regulation, the expression of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) 1 and 2 isoforms was investigated in human naïve (CD45RA+) and memory (CD45RO+) CD4+ T cells. Stimulation of both types of cells via the CD3/CD28 pathway resulted in high expression of both PPARγ receptors as measured by real-time PCR. Treatment with the PPARγ agonist, ciglitazone, increased PPARγ1 expression but decreased PPARγ2 expression in stimulated naïve and memory cells. Furthermore, when present, the magnitude of both PPARγ receptors expression was lower in naïve cells, perhaps suggesting a lower regulatory control of these cells. Similar profiles of selected proinflammatory cytokines were expressed by the two cell types following stimulation. The induction of PPARγ1 and suppression of PPARγ2 expressions in naïve and memory CD4+ T cells in the presence of ciglitazone suggest that the PPARγ subtypes may have different roles in the regulation of T-cell function.
    Matched MeSH terms: Gene Expression Regulation/immunology
  14. Ching JJ, Shuib AS, Abdullah N, Majid NA, Taufek NM, Sutra J, et al.
    Fish Shellfish Immunol, 2021 Sep;116:61-73.
    PMID: 34157396 DOI: 10.1016/j.fsi.2021.06.005
    In aquaculture, commercial fish such as red hybrid tilapia are usually raised at high density to boost the production within a short period of time. This overcrowded environment, however, may cause stress to the cultured fish and increase susceptibility to infectious diseases. Antibiotics and chemotherapeutics are used by fish farmers to overcome these challenges, but this may increase the production cost. Studies have reported on the potential of mushroom polysaccharides that can act as immunostimulants to enhance the immune response and disease resistance in fish. In the current study, hot water extract (HWE) from mushroom stalk waste (MSW) was used to formulate fish feed and hence administered to red hybrid tilapia to observe the activation of immune system. Upon 30 days of feeding, the fish were challenged with pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharides (LPS) and polyinosinic:polycytidylic acid (poly (I:C)) to mimic bacterial and viral infection, respectively. HWE supplementation promoted better feed utilisation in red hybrid tilapia although it did not increase the body weight gain and specific growth rate compared to the control diet. The innate immunological parameters such as phagocytic activity and respiratory burst activity were significantly higher in HWE-supplemented group than that of the control group following PAMPs challenges. HWE-supplemented diet also resulted in higher mRNA transcription of il1b and tnfa in midgut, spleen and head kidney at 1-day post PAMPs injection. Tlr3 exhibited the highest upregulation in the HWE fed fish injected with poly (I:C). At 3-days post PAMPs injection, both ighm and tcrb expression were upregulated significantly in the spleen and head kidney. Results showed that HWE supplementation enhances the immune responses of red hybrid tilapia and induced a higher serum bactericidal activity against S. agalactiae.
    Matched MeSH terms: Gene Expression Regulation/immunology
  15. Jahromi MZ, Bello MB, Abdolmaleki M, Yeap SK, Hair-Bejo M, Omar AR
    Dev Comp Immunol, 2018 10;87:116-123.
    PMID: 29886054 DOI: 10.1016/j.dci.2018.06.004
    To gain insights into the role of CD3-/28.4+ intraepithelial lymphocytes-natural killer (CD3-/28.4+IEL-NK) cells during infectious bursal disease virus (IBDV) infection, characterisation of the cells was performed following infection with different strains of the virus. In vitro treatment with IL-18 or ionomycin/PMA successfully stimulated and activated the cells via a significant increase in the expression of CD69, B-Lec, CHIR-AB1 and NK-lysin. Similarly, chickens infected with the vaccine strain of IBDV also up-regulated the expression of CD69, B-Lec, CHIR-AB1 and NK-lysin in CD3-/28.4+ IEL-NK cells up to 3 days post infection (dpi) and down-regulated the expression of the inhibitory receptor B-NK at 3 dpi. On the contrary, infection with the very virulent IBDV (vvIBDV) strain lead to a reduced activation of the cells by down-regulating the expression of the CD69, CHIR-AB1 and NK-lysin especially at 1 dpi. These findings altogether demonstrate the differential activation of CD3-/28.4+IEL-NK cells in chicken following infection with the vaccine or very virulent strains of IBDV. The study therefore provides an important clue into the differential pathogenesis of IBDV infection in chicken. Further studies are however required to determine the functional importance of these findings during IBDV vaccination and infection.
    Matched MeSH terms: Gene Expression Regulation/immunology
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