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https://www.readbyqxmd.com/read/28934427/immunologic-profiling-of-human-metapneumovirus-for-the-development-of-targeted-immunotherapy
#1
Ifigeneia Tzannou, Sarah K Nicholas, Premal Lulla, Paibel I Aguayo-Hiraldo, Anisha Misra, Caridad A Martinez, Annette A Machado, Jordan S Orange, Pedro A Piedra, Juan F Vera, Ann M Leen
Human metapneumovirus (hMPV) is a respiratory virus detected in ≥9% of allogeneic hematopoietic stem cell transplant (HSCT) recipients, in whom it can cause significant morbidity and mortality. Given the lack of effective antivirals, we investigated the potential for immunotherapeutic intervention, using adoptively transferred T cells. Thus, we characterized the cellular immune response to the virus and identified F, N, M2-1, M, and P as immunodominant target antigens. Reactive T cells were polyclonal (ie, they expressed CD4 and CD8), T-helper type 1 polarized, and polyfunctional (ie, they produced interferon γ, tumor necrosis factor α, granulocyte-macrophage colony-stimulating factor, and granzyme B), and they were able to kill autologous antigen-loaded targets...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28932321/identification-and-characterization-of-interferon-signaling-related-micrornas-in-occult-hepatitis-b-virus-infection
#2
Yiying Wang, Peifu Zhu, Jing Qiu, Jie Wang, Huijuan Zhu, Yinwei Zhu, Lige Zhang, Jie Zhu, Xingxiang Liu, Chen Dong
BACKGROUND: Occult hepatitis B virus infection (OBI) is an important risk factor of liver cirrhosis and hepatocellular carcinoma. Type 1 interferon (IFN) signaling-related miRNAs were significantly associated with hepatitis B virus (HBV) infection. However, the characteristics of serum IFN signaling-related miRNAs in OBI remain unclear. Therefore, this study aimed to analyze the expression levels of serum IFN signaling-related miRNAs in OBI and to evaluate their potential values for OBI diagnosis...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28929635/association-between-interferon-induced-helicase-ifih1-rs1990760-polymorphism-and-seasonal-variation-in-the-onset-of-type-1-diabetes-mellitus-ifih1-polymorphism-and-type-1-diabetes-onset
#3
Ágnes Jermendy, Ildikó Szatmári, Anna Körner, Attila J Szabó, Péter Tóth-Heyn, Róbert Hermann
BACKGROUND: Infections, mostly of viral origin, may contribute to the seasonal variation in the onset of type 1 diabetes mellitus (T1DM). The rs1990760 (A>G, Ala946Thr) polymorphism (GG genotype) of the interferon induced helicase (IFIH1), a virus recognition receptor, confers a modest protection for T1DM. The aim of our study was to evaluate a possible association between this IFIH1 polymorphism and the seasonal variation in the onset of T1DM. MATERIALS AND METHODS: The IFIH1 rs1990760 polymorphism was genotyped in 1055 patients of Central-Eastern European ancestry with T1DM (median age at diagnosis: 8...
September 20, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28929138/cryoem-structure-of-mxb-reveals-a-novel-oligomerization-interface-critical-for-hiv-restriction
#4
Frances J D Alvarez, Shaoda He, Juan R Perilla, Sooin Jang, Klaus Schulten, Alan N Engelman, Sjors H W Scheres, Peijun Zhang
Human dynamin-like, interferon-induced myxovirus resistance 2 (Mx2 or MxB) is a potent HIV-1 inhibitor. Antiviral activity requires both the amino-terminal region of MxB and protein oligomerization, each of which has eluded structural determination due to difficulties in protein preparation. We report that maltose binding protein-fused, full-length wild-type MxB purifies as oligomers and further self-assembles into helical arrays in physiological salt. Guanosine triphosphate (GTP), but not guanosine diphosphate, binding results in array disassembly, whereas subsequent GTP hydrolysis allows its reformation...
September 2017: Science Advances
https://www.readbyqxmd.com/read/28927906/il-17a-contributes-to-reducing-ifn-%C3%AE-il-4-ratio-and-persistence-of-entamoeba-histolytica-during-intestinal-amebiasis
#5
Sharmina Deloer, Risa Nakamura, Mihoko Kikuchi, Taeko Moriyasu, Yombo Dan Justin Kalenda, Eman Sayed Mohammed, Masachika Senba, Yoichiro Iwakura, Hiroki Yoshida, Shinjiro Hamano
Amebiasis is an infectious disease caused by Entamoeba histolytica, an anaerobic protozoan parasite, and is a major public health problem worldwide, particularly in areas with inadequate sanitation and poor hygiene. Th1 responses, represented by interferon gamma (IFN-γ), play a protective role by clearing the amebae from the gut, whereas Th2 responses are responsible for chronic infection. Th17 responses preconditioned by vaccination or by modulating the intestinal microbiome protect mice from the settlement of E...
September 16, 2017: Parasitology International
https://www.readbyqxmd.com/read/28926602/autoimmune-disease-mouse-model-exhibits-pulmonary-arterial-hypertension
#6
Koichi Sugimoto, Kazuhiko Nakazato, Akihiko Sato, Satoshi Suzuki, Akiomi Yoshihisa, Takeshi Machida, Shu-Ichi Saitoh, Hideharu Sekine, Yasuchika Takeishi
BACKGROUND: Pulmonary arterial hypertension is often associated with connective tissue disease. Although there are some animal models of pulmonary hypertension, an autoimmune disease-based model has not yet been reported. MRL/lpr mice, which have hypergammaglobulinemia, produce various autoimmune antibodies, and develop vasculitis and nephritis spontaneously. However, little is known about pulmonary circulation in these mice. In the present study, we examined the pulmonary arterial pressure in MRL/lpr mice...
2017: PloS One
https://www.readbyqxmd.com/read/28923396/smac-mimetics-and-type-ii-interferon-synergistically-induce-necroptosis-in-various-cancer-cell-lines
#7
Michael John Cekay, Stefanie Roesler, Tanja Frank, Anne-Kathrin Knuth, Ines Eckhardt, Simone Fulda
Since cancer cells often evade apoptosis, induction of necroptosis as another mode of programmed cell death is considered as a promising therapeutic alternative. Here, we identify a novel synergistic interaction of Smac mimetics that antagonize x-linked Inhibitor of Apoptosis (XIAP), cellular Inhibitor of Apoptosis (cIAP) 1 and 2 with interferon (IFN)γ to induce necroptosis in apoptosis-resistant cancer cells in which caspase activation is blocked. The synergistic is confirmed by calculation of combination indices (CIs) and found in both solid and hematological cancer cell lines as well as for different Smac mimetics (i...
September 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28919775/investigation-of-proliferation-and-migration-of-tongue-squamous-cell-carcinoma-promoted-by-three-chemokines-mip-3%C3%AE-mip-1%C3%AE-and-ip-10
#8
Hongxing Chu, Bo Jia, Xiaoling Qiu, Jie Pan, Xiang Sun, Zhiping Wang, Jianjiang Zhao
The aim of this work was to investigate the role of chemokines in proliferation and migration of tongue squamous cell carcinoma (TSCC). Out of the 80 cytokines surveyed by a human cytokine antibody array, three chemokines, macrophage inflammatory protein-3α (MIP-3α), macrophage inflammatory protein-1β (MIP-1β), and interferon gamma-induced protein 10 (IP-10), showed elevated expression in TSCC cells (CAL-27 and UM-1), compared to the oral mucosal epithelial cells. Immunohistochemistry confirmed the high level of expression of MIP-3α in the TSCC tissues, especially in the high clinical stages...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28919446/increased-interferon-mediated-immunity-following-in-vitro-and-in-vivo-modafinil-treatment-on-peripheral-immune-cells
#9
Adriano Zager, Wesley Nogueira Brandão, Rafael Oliveira Margatho, Daniel Sanzio Gimenes Cruz, Jean Pierre Peron, Sergio Tufik, Monica Levy Andersen, Monica Moresco, Fabio Pizza, Giuseppe Plazzi, Birgitte Rahbek Kornum, João Palermo-Neto
The wake-promoting drug Modafinil has been used for treatment of sleep disorders, such as Narcolepsy, excessive daytime sleepiness and sleep apnea, due to its stimulant action. Despite the known effect of Modafinil on brain neurochemistry, particularly on brain dopamine system, recent evidence support an immunomodulatory role for Modafinil treatment in neuroinflammatory models. Here, we aimed to study the effects of in vitro and in vivo Modafinil treatment on activation, proliferation, cell viability, and cytokine production by immune cells in splenocytes culture from mice...
September 15, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28916184/role-of-the-il-12-il-35-balance-in-sj%C3%A3-gren-s-syndrome
#10
Olivier Fogel, Elodie Rivière, Raphaèle Seror, Gaetane Nocturne, Saida Boudaoud, Bineta Ly, Jacques-Eric Gottenberg, Véronique Le Guern, Jean-Jacques Dubost, Joanne Nititham, Kimberly E Taylor, Philippe Chanson, Philippe Dieudé, Lindsey A Criswell, Bernd Jagla, Alice Thai, Michael Mingueneau, Xavier Mariette, Corinne Miceli-Richard
BACKGROUND: An interferon (IFN) signature is involved in the pathogenesis of primary Sjögren's syndrome (pSS), but whether the signature is type 1 or 2 remains controversial. Mouse models and genetic studies suggested the involvement of T helper 1 and type 2 IFN pathways. Likewise, polymorphisms of interleukin 12A gene (IL-12A), which encodes for IL-12p35, have been associated with pSS. IL-12p35 subunit is shared by 2 heterodimers, IL-12 and IL-35. OBJECTIVE: To confirm the genetic association of IL-12A polymorphism and pSS and elucidate the involvement of the IL-12/IL-35 balance in pSS by functional studies...
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28915148/adult-fmr1-knockout-mice-present-with-deficiencies-in-hippocampal-interleukin-6-and-tumor-necrosis-factor-%C3%AE-expression
#11
Samantha L Hodges, Suzanne O Nolan, Joseph H Taube, Joaquin N Lugo
Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a single genetic mutation in the FMR1 gene. Mutations in the FMR1 gene are the largest monogenic cause of autism spectrum disorder (ASD), and thus both disorders share many of the same cognitive and behavioral impairments. There is increasing evidence suggesting that dysregulated immune responses play a role in the pathophysiology of ASD; however, the association between FXS and altered immunity requires further investigation. This study examined whether Fmr1 knockout (KO) and wild-type mice on a FVB/NJ background strain had altered cytokine expression at baseline levels in the hippocampus...
September 14, 2017: Neuroreport
https://www.readbyqxmd.com/read/28914637/signal-transducer-and-activator-of-transcription-gain-of-function-primary-immunodeficiency-immunodysregulation-disorders
#12
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/28912844/triptolide-inhibits-cd4-memory-t-cell-mediated-acute-rejection-and-prolongs-cardiac-allograft-survival-in-mice
#13
Shuiwei Qiu, Dingliang Lv
There have been numerous investigations into the immunosuppressive effects of triptolide; however, its inhibitory effects on memory T cells remain to be elucidated. Using a cluster of differentiation (CD)4(+) memory T-cell transfer model, the aim of the present study was to determine the inhibitory effects of triptolide on CD4(+) memory T cell-mediated acute rejection and to determine the potential underlying mechanisms. At 4 weeks after skin transplantation, mouse cervical heart transplantation was performed following the transfer of CD4(+) memory T cells...
October 2017: Experimental and Therapeutic Medicine
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
#14
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/28912267/antitumor-immunity-is-defective-in-t-cell-specific-microrna-155-deficient-mice-and-is-rescued-by-immune-checkpoint-blockade
#15
Thomas B Huffaker, Soh-Hyun Lee, William W Tang, Jared A Wallace, Margaret Alexander, Marah C Runtsch, Dane K Larsen, Jacob Thompson, Andrew G Ramstead, Warren P Voth, Ruozhen Hu, June L Round, Matthew A Williams, Ryan M O'Connell
MicroRNA-155 (miR-155) regulates antitumor immune responses. However, its specific functions within distinct immune cell types have not been delineated in conditional knockout (KO) mouse models. In this study, we investigated the role of miR-155 specifically within T cells during the immune response to syngeneic tumors. We found that miR-155 expression within T cells is required to limit syngeneic tumor growth and promote interferon gamma (IFNγ) production by T cells within the tumor microenvironment. Consequently, we found that miR-155 expression by T cells is necessary for proper tumor-associated macrophage (TAM) expression of IFNγ-inducible genes...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28912017/indoleamine-2-3-dioxygenase-1-increased-in-human-gastric-pre-neoplasia-promotes-inflammation-and-metaplasia-in-mice-and-is-associated-with-type-ii-hypersensitivity-autoimmunity
#16
Mohamad El-Zaatari, Adam J Bass, Reanne Bowlby, Min Zhang, Li-Jyun Syu, Yitian Yang, Helmut Grasberger, Andrew Shreiner, Bei Tan, Shrinivas Bishu, Wai K Leung, Andrea Todisco, Nobuhiko Kamada, Marilia Cascalho, Andrzej A Dlugosz, John Y Kao
BACKGROUND & AIMS: Chronic gastrointestinal inflammation increases the risk of cancer by mechanisms that are not well understood. Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-binding enzyme that regulates the immune response via catabolization and regulation of tryptophan availability for immune cell uptake. IDO1 expression is increased during the transition from chronic inflammation to gastric metaplasia. We investigated whether IDO1 contributes to the inflammatory response that mediates loss of parietal cells leading to metaplasia...
September 11, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28911151/expanding-the-phenotypic-and-genotypic-landscape-of-autoimmune-polyendocrine-syndrome-type-1
#17
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/28904198/type-1-interferon-signalling-to-dendritic-cells-limits-murid-herpesvirus-4-spread-from-the-olfactory-epithelium
#18
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
#19
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/28903779/hepatitis-delta-virological-and-clinical-aspects
#20
REVIEW
Luan Felipo Botelho-Souza, Mariana Pinheiro Alves Vasconcelos, Alcione de Oliveira Dos Santos, Juan Miguel Villalobos Salcedo, Deusilene Souza Vieira
There are an estimated 400 million chronic carriers of HBV worldwide; between 15 and 20 million have serological evidence of exposure to HDV. Traditionally, regions with high rates of endemicity are central and northern Africa, the Amazon Basin, eastern Europe and the Mediterranean, the Middle East and parts of Asia. There are two types of HDV/HBV infection which are differentiated by the previous status infection by HBV for the individual. Individuals with acute HBV infection contaminated by HDV is an HDV/HBV co-infection, while individuals with chronic HBV infection contaminated by HDV represent an HDV/HBV super-infection...
September 13, 2017: Virology Journal
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