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https://www.readbyqxmd.com/read/28095439/intracranial-injection-of-dengue-virus-induces-interferon-stimulated-genes-and-cd8-t-cell-infiltration-by-sphingosine-kinase-1-independent-pathways
#1
Wisam H Al-Shujairi, Jennifer N Clarke, Lorena T Davies, Mohammed Alsharifi, Stuart M Pitson, Jillian M Carr
We have previously reported that the absence of sphingosine kinase 1 (SK1) affects both dengue virus (DENV) infection and innate immune responses in vitro. Here we aimed to define SK1-dependancy of DENV-induced disease and the associated innate responses in vivo. The lack of a reliable mouse model with a fully competent interferon response for DENV infection is a challenge, and here we use an experimental model of DENV infection in the brain of immunocompetent mice. Intracranial injection of DENV-2 into C57BL/6 mice induced body weight loss and neurological symptoms which was associated with a high level of DENV RNA in the brain...
2017: PloS One
https://www.readbyqxmd.com/read/28092673/irf7-regulates-the-development-of-granulocytic-myeloid-derived-suppressor-cells-through-s100a9-transrepression-in-cancer
#2
Q Yang, X Li, H Chen, Y Cao, Q Xiao, Y He, J Wei, J Zhou
Accumulation of myeloid-derived suppressor cells (MDSCs) is one of the major obstacles against achieving appropriate anti-tumor immune responses and successful tumor immunotherapy. Granulocytic MDSCs (G-MDSCs) are common in tumor-bearing hosts. However, the mechanisms regulating the development of MDSCs, especially G-MDSCs, remain poorly understood. In this report, we showed that interferon regulatory factor 7 (IRF7) plays an important role in the development of G-MDSCs, but not monocytic MDSCs. IRF7 deficiency caused significant elevation of G-MDSCs, and therefore enhanced tumor growth and metastasis in mice...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28077651/bromodomain-containing-4-brd4-couples-nf%C3%AE%C2%BAb-rela-with-airway-inflammation-and-the-irf-rig-i-amplification-loop-in-respiratory-syncytial-virus-infection
#3
Bing Tian, Jun Yang, Yingxin Zhao, Teodora Ivanciuc, Hong Sun, Roberto P Garofalo, Allan R Brasier
: The airway mucosa expresses protective interferon (IFN) and inflammatory cytokines in response to Respiratory Syncytial Virus (RSV) infection. In this study, we examine the role of bromodomain containing 4 (BRD4) in mediating this innate immune response in human small airway epithelial cells. We observe that RSV induces BRD4 to complex with NFκB/RelA. BRD4 is functionally required for expression of the NFκB-dependent inflammatory gene regulatory network (GRN), including the IFN Response Factor (IRFs)-1 and -7 that mediate a cross-talk pathway for RIG-I upregulation...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28027521/correlation-between-severe-infection-and-breast-cancer-metastases-in-the-eortc-10994-big-1-00-trial-investigating-innate-immunity-as-a-tumour-suppressor-in%C3%A2-breast-cancer
#4
Nathan Touati, Konstantinos Tryfonidis, Franco Caramia, Hervé Bonnefoi, David Cameron, Leen Slaets, Belinda S Parker, Sherene Loi
BACKGROUND: Breast cancer cells which express an innate immune signature regulated by interferon regulatory factor 7 (IRF7) have reduced metastatic potential. Infections can induce interferon signalling and may activate an anti-tumour immune response. We investigated whether 'severe infection' can be a clinical surrogate of this phenomenon and/or the presence of high levels of the IRF7 signature at diagnosis before neo-adjuvant chemotherapy (NACT) is associated with a reduced distant relapse risk, specifically in bones...
December 24, 2016: European Journal of Cancer
https://www.readbyqxmd.com/read/28012987/characterization-of-non-lethal-west-nile-virus-wnv-infection-in-horses-subclinical-pathology-and-innate-immune-response
#5
Helle Bielefeldt-Ohmann, Angela Bosco-Lauth, Airn-Elizabeth Hartwig, M Jasim Uddin, Jean Barcelon, Willy W Suen, Wenqi Wang, Roy A Hall, Richard A Bowen
Most natural West Nile virus (WNV) infections in humans and horses are subclinical or sub-lethal and non-encephalitic. Yet, the main focus of WNV research remains on the pathogenesis of encephalitic disease, mainly conducted in mouse models. We characterized host responses during subclinical WNV infection in horses and compared outcomes with those obtained in a novel rabbit model of subclinical WNV infection (Suen et al. 2015. Pathogens, 4: 529). Experimental infection of 10 horses with the newly emerging WNV-strain, WNVNSW2011, did not result in neurological disease in any animal but transcriptional upregulation of both type I and II interferon (IFN) was seen in peripheral blood leukocytes prior to or at the time of viremia...
December 21, 2016: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27980081/ddx3-directly-regulates-traf3-ubiquitination-and-acts-as-a-scaffold-to-coordinate-assembly-of-signalling-complexes-downstream-of-mavs
#6
Lili Gu, Anthony Fullam, Niamh McCormack, Yvette Hoehn, Martina Schroeder
Human DEAD-box helicase 3 (DDX3) has been shown to contribute to type I interferon induction downstream of anti-viral pattern recognition receptors (PRRs). It binds to TANK-binding kinase 1 (TBK1) and IκB-kinase-ε (IKKε), the two key kinases mediating activation of Interferon regulatory factor (IRF) 3 and IRF7. We previously demonstrated that DDX3 facilitates IKKε activation downstream of RIG-I and then links the activated kinase to IRF3. In this study, we probed the interactions between DDX3 and other key signalling molecules in the RIG-I pathway and identified a novel direct interaction between DDX3 and TRAF3 mediated by a TRAF-interaction motif in the N-terminus of DDX3, which was required for TRAF3 ubiquitination...
December 15, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27903798/lubac-modulates-lmp1-activation-of-nf%C3%AE%C2%BAb-and-irf7
#7
Ling Wang, Yujia Wang, Juan Zhao, Junping Ren, Kenton H Hall, Jonathan P Moorman, Zhi Q Yao, Shunbin Ning
: Recently, Linear Ubiquitin Assembly Complex (LUBAC)-mediated linear ubiquitination has come into focus due to its emerging role in activation of NFκB in different biological contexts. However, the role of LUBAC in LMP1 signaling leading to NFκB and IRF7 activation has not been investigated. We have shown here that RNF31, the key component of LUBAC complex, interacts with LMP1 and IRF7 in EBV-transformed cells, and that LUBAC stimualtes linear ubiquitination of NEMO and IRF7. Consequently, LUBAC is required for LMP1 signaling to full activation of NFκB, but inhibits LMP1-stimulated IRF7 transcriptional activity...
November 30, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27864558/prospective-study-of-the-innate-cellular-immune-response-in-low-vaccine-responder-children
#8
Naveen Surendran, Ted Nicolosi, Ravinder Kaur, Matthew Morris, Michael Pichichero
We recently reported our findings from a longitudinal, prospective study where we identified 10% infants who were low vaccine responders (LVR) at age 9-12 mo following routine primary series vaccine schedule. We found multiple cellular deficiencies in LVR children, including low number of memory B cells, reduced polyclonal stimulation of naïve/memory T cell response and suboptimal APC response. These children outgrew their poor vaccine response by the time they received booster doses of vaccine. Studies in human infant innate immunity are rare because of the unique challenges in specimen collection...
November 18, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27847343/fish-trim32-functions-as-a-critical-antiviral-molecule-against-iridovirus-and-nodavirus
#9
Yepin Yu, Xiaohong Huang, Jiaxin Liu, Jingcheng Zhang, Yin Hu, Ying Yang, Youhua Huang, Qiwei Qin
Tripartite motif-containing 32 (TRIM32) has been demonstrated to pay vital roles in cancer, genetic disorders and antiviral immunity. However, the molecular functions of fish TRIM32 still remained largely unknown. Here, a novel TRIM32 gene from orange spotted grouper (EcTRIM32) was cloned and characterized. EcTRIM32 encoded a 685-aa protein which showed 93%, and 60% identity to large yellow croaker (Larimichthys crocea) and human (Homo sapiens), respectively. Amino acid alignment showed that EcTRIM32 contained a conserved RING-finger domain, a BBOX domain and NHL domain...
November 12, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27822537/a-simple-screening-approach-to-prioritize-genes-for-functional-analysis-identifies-a-role-for-interferon-regulatory-factor-7-in-the-control-of-respiratory-syncytial-virus-disease
#10
Jacqueline U McDonald, Myrsini Kaforou, Simon Clare, Christine Hale, Maria Ivanova, Derek Huntley, Marcus Dorner, Victoria J Wright, Michael Levin, Federico Martinon-Torres, Jethro A Herberg, John S Tregoning
Greater understanding of the functions of host gene products in response to infection is required. While many of these genes enable pathogen clearance, some enhance pathogen growth or contribute to disease symptoms. Many studies have profiled transcriptomic and proteomic responses to infection, generating large data sets, but selecting targets for further study is challenging. Here we propose a novel data-mining approach combining multiple heterogeneous data sets to prioritize genes for further study by using respiratory syncytial virus (RSV) infection as a model pathogen with a significant health care impact...
May 2016: MSystems
https://www.readbyqxmd.com/read/27815423/zebrafish-foxo3b-negatively-regulates-antiviral-response-through-suppressing-the-transactivity-of-irf3-and-irf7
#11
Xing Liu, Xiaolian Cai, Dawei Zhang, Chenxi Xu, Wuhan Xiao
Forkhead box O (FOXO)3, a member of the FOXO family of transcription factors, plays key roles in various cellular processes, including development, longevity, reproduction, and metabolism. Recently, FOXO3 has also been shown to be involved in modulating the immune response. However, how FOXO3 regulates immunity and the underlying mechanisms are still largely unknown. In this study, we show that zebrafish (Danio rerio) foxo3b, an ortholog of mammalian FOXO3, is induced by polyinosinic-polycytidylic acid stimulation and spring viremia of carp virus (SVCV) infection...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27815200/fish-trim16l-exerts-negative-regulation-on-antiviral-immune-response-against-grouper-iridoviruses
#12
Yepin Yu, Xiaohong Huang, Jingcheng Zhang, Jiaxi Liu, Yin Hu, Ying Yang, Jia Cai, Youhua Huang, Qiwei Qin
Tripartite motif 16 (TRIM16), has been demonstrated to act as a tumor suppressor through affecting cell proliferation and migration or tumorigenicity in carcigenesis. However, the roles of TRIM16 in immune response were unknown up to now. Here, we cloned a TRIM16-like gene (TRIM16L) from orange spotted grouper (EcTRIM16L) and investigated its roles in response to virus infection. EcTRIM16L encoded a 478 amino acid peptide which showed 72% and 29% identity to large yellow croaker (Larimichthys crocea) and human (Homo sapiens), respectively...
December 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27811478/deletion-of-irf3-and-irf7-genes-in-mice-results-in-altered-interferon-pathway-activation-and-granulocyte-dominated-inflammatory-responses-to-influenza-a-infection
#13
Bastian Hatesuer, Hang Thi Thu Hoang, Peggy Riese, Stephanie Trittel, Ingo Gerhauser, Husni Elbahesh, Robert Geffers, Esther Wilk, Klaus Schughart
The interferon (IFN) pathway plays an essential role in the innate immune response following viral infections and subsequent shaping of adaptive immunity. Infections with influenza A viruses (IAV) activate the IFN pathway after the recognition of pathogen-specific molecular patterns by respective pattern recognition receptors. The IFN regulatory factors IRF3 and IRF7 are key players in the regulation of type I and III IFN genes. In this study, we analyzed the role of IRF3 and IRF7 for the host response to IAV infections in Irf3-/-, Irf7-/-, and Irf3-/-Irf7-/- knockout mice...
November 4, 2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/27793594/cross-regulation-of-two-type-i-interferon-signaling-pathways-in-plasmacytoid-dendritic-cells-controls-anti-malaria-immunity-and-host-mortality
#14
Xiao Yu, Baowei Cai, Mingjun Wang, Peng Tan, Xilai Ding, Jian Wu, Jian Li, Qingtian Li, Pinghua Liu, Changsheng Xing, Helen Y Wang, Xin-Zhuan Su, Rong-Fu Wang
Type I interferon (IFN) is critical for controlling pathogen infection; however, its regulatory mechanisms in plasmacytoid cells (pDCs) still remain unclear. Here, we have shown that nucleic acid sensors cGAS-, STING-, MDA5-, MAVS-, or transcription factor IRF3-deficient mice produced high amounts of type I IFN-α and IFN-β (IFN-α/β) in the serum and were resistant to lethal plasmodium yoelii YM infection. Robust IFN-α/β production was abolished when gene encoding nucleic acid sensor TLR7, signaling adaptor MyD88, or transcription factor IRF7 was ablated or pDCs were depleted...
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27763806/rnaseq-reveals-hypervirulence-specific-host-responses-to-m-tuberculosis-infection
#15
Gina Leisching, Ray-Dean Pietersen, Carel van Heerden, Paul van Helden, Ian Wiid, Bienyameen Baker
The distinguishing factors that characterize the host response to infection with virulent Mycobacterium tuberculosis (M.tb) are largely confounding. We present an infection study with two genetically closely related M.tb strains that have vastly different pathogenic characteristics. The early host response to infection with these detergent-free cultured strains was analysed through RNAseq in an attempt to provide information on the subtleties which may ultimately contribute to the virulent phenotype. Murine bone marrow derived macrophages (BMDMs) were infected with either a hyper- (R5527) or hypovirulent (R1507) Beijing M...
October 20, 2016: Virulence
https://www.readbyqxmd.com/read/27733217/overexpression-of-interferon-regulatory-factor-7-irf7-reduces-bone-metastasis-of-prostate-cancer-cells-in-mice
#16
Yang Zhao, Wenxia Chen, Weiliang Zhu, Hui Meng, Jie Chen, Jian Zhang
The purpose of this study was to identify the role of interferon regulatory factor 7 (IRF7) in the bone metastasis of prostate cancer. Herein, we demonstrated the lower expression of IRF7 in bone metastases of prostate cancer. Overexpression of IRF7 in prostate cancer cells had a marked effect on inhibiting bone metastases but not on tumor growth in xenograft nude mice. While in vitro, up-regulation of IRF7 had little effect on the malignant phenotype of prostate cancer cells including proliferation, apoptosis, migration, and invasion...
October 11, 2016: Oncology Research
https://www.readbyqxmd.com/read/27697837/nfatc3-promotes-irf7-transcriptional-activity-in-plasmacy-toid-dendritic-cells
#17
Musheng Bao, York Wang, Ying Liu, Peiqing Shi, Hongbo Lu, Wenwen Sha, Leiyun Weng, Shino Hanabuchi, Jun Qin, Joel Plumas, Laurence Chaperot, Zhiqiang Zhang, Yong-Jun Liu
Plasmacytoid dendritic cells (pDCs) rapidly produce large amounts of type 1 interferon (IFN) after Toll-like receptor 7 and 9 engagements. This specialized function of type 1 IFN production is directly linked to the constitutive expression of IRF7, the master transcription factor for type 1 IFN production. However, the IRF7 regulatory network in pDCs remains largely unknown. In this study, we identify that the transcription factor NFATC3 specifically binds to IRF7 and enhances IRF7-mediated IFN production. Furthermore, knockout of NFATC3 greatly reduced the CpG DNA-induced nuclear translocation of IRF7, which resulted in impaired type 1 IFN production in vitro and in vivo...
October 17, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27688705/lps-induced-expression-of-cd14-in-the-trif-pathway-is-epigenetically-regulated-by-sulforaphane-in-porcine-pulmonary-alveolar-macrophages
#18
Qin Yang, Maren J Pröll, Dessie Salilew-Wondim, Rui Zhang, Dawit Tesfaye, Huitao Fan, Mehmet U Cinar, Christine Große-Brinkhaus, Ernst Tholen, Mohammad A Islam, Michael Hölker, Karl Schellander, Muhammad J Uddin, Christiane Neuhoff
Pulmonary alveolar macrophages (AMs) are important in defense against bacterial lung inflammation. Cluster of differentiation 14 (CD14) is involved in recognizing bacterial lipopolysaccharide (LPS) through MyD88-dependent and TRIF pathways of innate immunity. Sulforaphane (SFN) shows anti-inflammatory activity and suppresses DNA methylation. To identify CD14 epigenetic changes by SFN in the LPS-induced TRIF pathway, an AMs model was investigated in vitro CD14 gene expression was induced by 5 µg/ml LPS at the time point of 12 h and suppressed by 5 µM SFN...
September 29, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27677680/expression-and-functional-characterization-of-interferon-regulatory-factors-irf2-irf7-and-irf9-in-the-blunt-snout-bream-megalobrama-amblycephala
#19
Fan-Bin Zhan, Han Liu, Rui-Fang Lai, Ivan Jakovlić, Wei-Min Wang
Interferon regulatory factors (irfs) are a family of genes that encode transcription factors with important roles in regulating the expression of Type I interferons (IFNs) and other genes associated with related pathways. irfs have multitudinous functions in growth, development and regulation of oncogenesis. In this study, three irf family members (irf2, irf7, irf9) were identified and characterized in Megalobrama amblycephala at the mRNA and amino acid levels. M. amblycephala irfs share a high sequence homology with other vertebrate irfs...
February 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/27667736/impaired-virus-replication-and-decreased-innate-immune-responses-to-viral-infections-in-nasal-epithelial-cells-from-patients-with-allergic-rhinitis
#20
A Głobińska, M Pawełczyk, A Piechota-Polańczyk, A Olszewska-Ziąber, S Moskwa, A Mikołajczyk, A Jabłońska, P K Zakrzewski, M Brauncajs, M Jarzębska, S Taka, N G Papadopoulos, M L Kowalski
The aim of this study was to assess the immune response to parainfluenza virus type 3 (PIV3), rhinovirus 1B (RV1B) and intracellular Toll-like receptors (TLR) agonists in nasal epithelial cells (NECs) from patients with allergic rhinitis and healthy controls. NECs were obtained from eight patients with allergic rhinitis (AR) and 11 non-atopic healthy controls (HC) by nasal scraping, grown to confluence and exposed to PIV3, RV1B infection or TLR-3 and TLR-7/8 agonists. Interferon (IFN)-λ1, IFN-α, IFN-β and regulated on activation, normal T expressed and secreted (RANTES) release into the cell culture supernatants was assessed at 8, 24 and 48 h upon infection or 8 and 24 h after stimulation with poly(I:C) and R848...
January 2017: Clinical and Experimental Immunology
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