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https://www.readbyqxmd.com/read/28922426/a-dna-vaccine-for-crimean-congo-hemorrhagic-fever-protects-against-disease-and-death-in-two-lethal-mouse-models
#1
Aura R Garrison, Charles J Shoemaker, Joseph W Golden, Collin J Fitzpatrick, John J Suschak, Michelle J Richards, Catherine V Badger, Carolyn M Six, Jacqueline D Martin, Drew Hannaman, Marko Zivcec, Eric Bergeron, Jeffrey W Koehler, Connie S Schmaljohn
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne virus capable of causing a severe hemorrhagic fever disease in humans. There are currently no licensed vaccines to prevent CCHFV-associated disease. We developed a DNA vaccine expressing the M-segment glycoprotein precursor gene of CCHFV and assessed its immunogenicity and protective efficacy in two lethal mouse models of disease: type I interferon receptor knockout (IFNAR-/-) mice; and a novel transiently immune suppressed (IS) mouse model. Vaccination of mice by muscle electroporation of the M-segment DNA vaccine elicited strong antigen-specific humoral immune responses with neutralizing titers after three vaccinations in both IFNAR-/- and IS mouse models...
September 18, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28921595/the-interplay-of-type-i-and-type-ii-interferons-in-murine-autoimmune-cholangitis-as-a-basis-for-sex-biased-autoimmunity
#2
Heekyong R Bae, Deborah L Hodge, Guo-Xiang Yang, Patrick S C Leung, Sathi Babu Chodisetti, Julio C Valencia, Michael Sanford, John M Fenimore, Ziaur S M Rahman, Koichi Tsuneyama, Gary L Norman, M Eric Gershwin, Howard A Young
We have reported a murine model of autoimmune cholangitis, generated by altering the AU rich element by deletion of the IFN-γ 3'UTR region (coined ARE-Del(-/-) ), that has striking similarities to human primary biliary cholangitis (PBC) with female predominance. Previously, we suggested that the gender bias of autoimmune cholangitis was secondary to intense and sustained type I and II IFN signaling. Based on this thesis, and to define the mechanisms that lead to portal inflammation, we specifically addressed the hypothesis that type I IFNs are the driver of this disease...
September 16, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28917654/the-anticancer-functions-of-rig-i-like-receptors-rig-i-and-mda5-and-their-applications-in-cancer-therapy
#3
REVIEW
Yuanbing Wu, Xinqiang Wu, Longhuo Wu, Xiangcai Wang, Zhiping Liu
Cancer is a major cause of death worldwide, and its incidence and mortality continuously increase in China. Nowadays, cancer heavily influences our health and constitutes enormous burden on society and families. Although there are many tools for cancer treatment, but the overall therapeutic effect is poor. In addition, cancer cells often develop resistance to therapy due to defective cell death or immune escape mechanisms. Therefore, it is a promising way for cancer treatment to effectively activate apoptosis and conquer immunosuppression...
August 31, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28915824/fucoidan-from-fucus-vesiculosus-suppresses-hepatitis-b-virus-replication-by-enhancing-extracellular-signal-regulated-kinase-activation
#4
Huifang Li, Junru Li, Yuan Tang, Lin Lin, Zhanglian Xie, Jia Zhou, Liyun Zhang, Xiaoyong Zhang, Xiaoshan Zhao, Zhengliang Chen, Daming Zuo
BACKGROUND: Hepatitis B virus (HBV) infection is a serious public health problem leading to cirrhosis and hepatocellular carcinoma. As the clinical utility of current therapies is limited, the development of new therapeutic approaches for the prevention and treatment of HBV infection is imperative. Fucoidan is a natural sulfated polysaccharide that extracted from different species of brown seaweed, which was reported to exhibit various bioactivities. However, it remains unclear whether fucoidan influences HBV replication or not...
September 16, 2017: Virology Journal
https://www.readbyqxmd.com/read/28914637/signal-transducer-and-activator-of-transcription-gain-of-function-primary-immunodeficiency-immunodysregulation-disorders
#5
Filippo Consonni, Laura Dotta, Francesca Todaro, Donatella Vairo, Raffaele Badolato
PURPOSE OF REVIEW: To describe primary immunodeficiencies caused by gain-of-function (GOF) mutations of signal transducer and activator of transcription (STAT) genes, a group of genetically determined disorders characterized by susceptibility to infections and, in many cases, autoimmune manifestations. RECENT FINDINGS: GOF mutations affecting STAT1 result in increased STAT tyrosine phosphorylation and secondarily increased response to STAT1-signaling cytokines, such as interferons...
September 13, 2017: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/28912382/versican-is-produced-by-trif-and-type-i-interferon-dependent-signaling-in-macrophages-and-contributes-to-fine-control-of-innate-immunity-in-lungs
#6
Mary Y Chang, Inkyung Kang, Michael Gale, Anne M Manicone, Michael G Kinsella, Kathleen R Braun, Tara Wigmosta, William C Parks, William A Altemeier, Thomas N Wight, Charles W Frevert
Growing evidence suggests that versican is important in the innate immune response to lung infection. Our goal was to understand the regulation of macrophage-derived versican and the role it plays in innate immunity. We first defined the signaling events that regulate versican expression using bone marrow derived macrophages (BMDM) from mice lacking specific Toll-like receptors (TLR), TLR adaptor molecules or the type I interferon receptor (IFNAR1). We show that LPS and polyinosinic-polycytidylic acid [Poly(I:C)] trigger a signaling cascade involving TLR3 or 4, the Trif adaptor, Type I interferons and IFNAR1, leading to increased expression of versican by macrophages and implicating versican as an interferon-stimulated gene...
September 14, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28911151/expanding-the-phenotypic-and-genotypic-landscape-of-autoimmune-polyendocrine-syndrome-type-1
#7
Elizaveta M Orlova, Leila S Sozaeva, Maria A Kareva, Bergithe E Oftedal, Anette S B Wolff, Lars Breivik, Ekaterina Y Zakharova, Olga N Ivanova, Olle Kämpe, Ivan I Dedov, Per M Knappskog, Valentina A Peterkova, Eystein S Husebye
Context: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene and characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Comprehensive characterizations of large patient cohorts are rare. Objective: To perform an extensive clinical, immunological, and genetic characterization of a large nationwide Russian APS-1 cohort...
September 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28910635/gestational-stage-and-ifn-%C3%AE-signaling-regulate-zikv-infection-in-utero
#8
Brett W Jagger, Jonathan J Miner, Bin Cao, Nitin Arora, Amber M Smith, Attila Kovacs, Indira U Mysorekar, Carolyn B Coyne, Michael S Diamond
Although Zika virus (ZIKV)-induced congenital disease occurs more frequently during early stages of pregnancy, its basis remains undefined. Using established type I interferon (IFN)-deficient mouse models of ZIKV transmission in utero, we found that the placenta and fetus were more susceptible to ZIKV infection at earlier gestational stages. Whereas ZIKV infection at embryonic day 6 (E6) resulted in placental insufficiency and fetal demise, infections at midstage (E9) resulted in reduced cranial dimensions, and infection later in pregnancy (E12) caused no apparent fetal disease...
September 13, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28910400/293texosome-mediated-mir-146a-transfer-suppresses-type-i-interferon-response-and-facilitates-ev71-infection
#9
Yuxuan Fu, Li Zhang, Fang Zhang, Ting Tang, Qi Zhou, Chunhong Feng, Yu Jin, Zhiwei Wu
Exosomes can transfer genetic materials between cells. Their roles in viral infections are beginning to be appreciated. Researches have shown that exosomes released from virus-infected cells contain a variety of viral and host cellular factors that are able to modulate recipient's cellular response and result in productive infection of the recipient host. Here, we showed that EV71 infection resulted in upregulated exosome secretion and differential packaging of the viral genomic RNA and miR-146a into exosomes...
September 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28910320/differential-gene-expression-following-tlr-stimulation-in-rag1-mutant-zebrafish-tissues-and-morphological-descriptions-of-lymphocyte-like-cell-populations
#10
Preeti J Muire, Larry A Hanson, Robert Wills, Lora Petrie-Hanson
In the absence of lymphocytes, rag1-/- mutant zebrafish develop protective immunity to bacteria. In mammals, induction of protection by innate immunity can be mediated by macrophages or natural killer (NK) cells. To elucidate potential responsive cell populations, we morphologically characterized lymphocyte-like cells (LLCs) from liver, spleen and kidney hematopoietic tissues. In fish, these cells include NK cells and Non-specific cytotoxic cells (NCCs). We also evaluated the transcriptional expression response of select genes that are important indicators of NK and macrophage activation after exposure to specific TLR ligands...
2017: PloS One
https://www.readbyqxmd.com/read/28904198/type-1-interferon-signalling-to-dendritic-cells-limits-murid-herpesvirus-4-spread-from-the-olfactory-epithelium
#11
Clara Lawler, Philip G Stevenson
Murid Herpesvirus-4 (MuHV-4) is a B cell-tropic gamma-herpesvirus that can be studied in vivo Despite viral evasion, type 1 interferons (IFN-I) limit its spread. After MuHV-4 inoculation into footpads, IFN-I protect lymph node subcapsular sinus macrophages (SSM) against productive infection; after peritoneal inoculation, they protect splenic marginal zone macrophages; and they limit MuHV-4 replication in the lungs. While invasive infections can test specific aspects of host colonization, it is important also to understand natural infection...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28904192/the-role-of-herpes-simplex-virus-type-1-%C3%AE-34-5-in-the-regulation-of-irf3-signaling
#12
Richard Manivanh, Jesse Mehrbach, David M Knipe, David A Leib
During viral infection, pattern recognition receptors (PRRs) and their associated adaptors recruit TANK-binding kinase 1 (TBK1) to activate interferon regulatory factor 3 (IRF3), resulting in production of type I interferons (IFNs). ICP0 and ICP34.5 are amongst the proteins encoded by herpes simplex virus 1 (HSV-1) that modulate type I IFN signaling. We constructed a recombinant virus (ΔXX) which lacks amino acids 87 - 106, a portion of the previously described TBK1-binding domain of the γ34.5 gene (D. Verpooten, Y...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28902841/cgas-senses-long-and-hmgb-tfam-bound-u-turn-dna-by-forming-protein-dna-ladders
#13
Liudmila Andreeva, Björn Hiller, Dirk Kostrewa, Charlotte Lässig, Carina C de Oliveira Mann, David Jan Drexler, Andreas Maiser, Moritz Gaidt, Heinrich Leonhardt, Veit Hornung, Karl-Peter Hopfner
Cytosolic DNA arising from intracellular pathogens triggers a powerful innate immune response. It is sensed by cyclic GMP-AMP synthase (cGAS), which elicits the production of type I interferons by generating the second messenger 2'3'-cyclic-GMP-AMP (cGAMP). Endogenous nuclear or mitochondrial DNA can also be sensed by cGAS under certain conditions, resulting in sterile inflammation. The cGAS dimer binds two DNA ligands shorter than 20 base pairs side-by-side, but 20-base-pair DNA fails to activate cGAS in vivo and is a poor activator in vitro...
September 13, 2017: Nature
https://www.readbyqxmd.com/read/28901270/reappraisal-of-antimalarials-in-interferonopathies-new-perspectives-for-old-drugs
#14
Elisa Piscianz, Eva Cuzzoni, Rajan Sharma, Alessandra Tesser, Pooja Sapra, Alberto Tommasini
The story of antimalarials as antinflammatory drugs dates back several centuries. Chinin, the extract of the Cinchona bark, has been exploited since the 18th century for its antimalarial and antifebrile properties. Later, during the Second World War, the broad use of antimalarials allowed arguing their antirheumatic effect on soldiers. Since then, these drugs have been broadly used to treat Systemic Lupus Erythematosus, but, only recently, have the molecular mechanisms of action been partly clarified. Inhibitory action on vacuole function and trafficking has been considered for decades the main mechanism of the action of antimalarials, affecting the activation of phagocytes and dendritic cells...
September 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28900831/-18-f-dpa-714-pet-imaging-reveals-global-neuroinflammation-in-zika-virus-infected-mice
#15
Kyle Kuszpit, Bradley S Hollidge, Xiankun Zeng, Robert G Stafford, Sharon Daye, Xiang Zhang, Falguni Basuli, Joseph W Golden, Rolf E Swenson, Darci R Smith, Thomas M Bocan
PURPOSE: The association of Zika virus (ZIKV) infection and development of neurological sequelae require a better understanding of the pathogenic mechanisms causing severe disease. The purpose of this study was to evaluate the ability and sensitivity of positron emission tomography (PET) imaging using [(18)F]DPA-714, a translocator protein (TSPO) 18 kDa radioligand, to detect and quantify neuroinflammation in ZIKV-infected mice. PROCEDURES: We assessed ZIKV-induced pathogenesis in wild-type C57BL/6 mice administered an antibody to inhibit type I interferon (IFN) signaling...
September 12, 2017: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/28900269/predicted-effects-of-observed-changes-in-the-mrna-and-microrna-transcriptome-of-lung-neutrophils-during-s-pneumoniae-pneumonia-in-mice
#16
John C Gomez, Hong Dang, Matthew Kanke, Robert S Hagan, Jason R Mock, Samir N P Kelada, Praveen Sethupathy, Claire M Doerschuk
The complex role of neutrophils in modulating the inflammatory response is increasingly appreciated. Our studies profiled the expression of mRNAs and microRNAs (miRs) in lung neutrophils in mice during S. pneumoniae pneumonia and performed in depth in silico analyses. Lung neutrophils were isolated 24 hours after intratracheal instillation of PBS or S. pneumoniae, and differentially expressed (DE) mRNAs and miRs were identified. Lung neutrophils from mice with S. pneumoniae pneumonia contained 4127 DE mRNAs, 36% of which were upregulated at least 2-fold...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28900038/socs1-is-an-inducible-negative-regulator-of-ifn-lambda-induced-gene-expression-in-vivo
#17
Tanja Blumer, Mairene Coto-Llerena, Francois H T Duong, Markus H Heim
Type I (α and β) and type III (λ) interferons (IFNs) are induced upon viral infection through host sensory pathways that activate IFN regulatory factors (IRFs) and nuclear factor κB. Secreted IFNs induce autocrine and paracrine signalling through the JAK-Stat pathway leading to the transcriptional induction of hundreds of IFN stimulated genes (ISGs), amongst them sensory pathway components such as cGAS, STING, RIG-I, MDA5 and the transcription factor IRF7 that enhance the induction of IFNαs and IFNλss...
September 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28899396/transcriptomic-meta-analysis-identifies-gene-expression-characteristics-in-various-samples-of-hiv-infected-patients-with-nonprogressive-disease
#18
Le-Le Zhang, Zi-Ning Zhang, Xian Wu, Yong-Jun Jiang, Ya-Jing Fu, Hong Shang
BACKGROUND: A small proportion of HIV-infected patients remain clinically and/or immunologically stable for years, including elite controllers (ECs) who have undetectable viremia (<50 copies/ml) and long-term nonprogressors (LTNPs) who maintain normal CD4(+) T cell counts for prolonged periods (>10 years). However, the mechanism of nonprogression needs to be further resolved. In this study, a transcriptome meta-analysis was performed on nonprogressor and progressor microarray data to identify differential transcriptome pathways and potential biomarkers...
September 12, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28898711/sjl-bone-marrow-derived-macrophages-do-not-have-irf3-mutations-and-are-highly-susceptible-to-theiler-s-virus-infection
#19
Kyung-No Son, Zhiguo Liang, Howard L Lipton
It is well known that SJL mice are susceptible to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease while C57BL6 (B6) and B10 mice are resistant, and H-2(s) on a B10 background (B10.S) contributes modestly to susceptibility. A recent study linked two IRF3 non-conservative mutations in SJL compared to B10.S mice to resistance to TMEV infection of SJL peritoneal-derived macrophages, an observation of practical interest in light of the central role of IRF3 transcription factor in the type I interferon (IFN) response...
September 9, 2017: Virology
https://www.readbyqxmd.com/read/28898289/trim32-tax1bp1-dependent-selective-autophagic-degradation-of-trif-negatively-regulates-tlr3-4-mediated-innate-immune-responses
#20
Qing Yang, Tian-Tian Liu, Heng Lin, Man Zhang, Jin Wei, Wei-Wei Luo, Yun-Hong Hu, Bo Zhong, Ming-Ming Hu, Hong-Bing Shu
Toll-like receptor (TLR)-mediated signaling are critical for host defense against pathogen invasion. However, excessive responses would cause harmful damages to the host. Here we show that deficiency of the E3 ubiquitin ligase TRIM32 increases poly(I:C)- and LPS-induced transcription of downstream genes such as type I interferons (IFNs) and proinflammatory cytokines in both primary mouse immune cells and in mice. Trim32-/- mice produced higher levels of serum inflammatory cytokines and were more sensitive to loss of body weight and inflammatory death upon Salmonella typhimurium infection...
September 2017: PLoS Pathogens
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