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https://www.readbyqxmd.com/read/29150899/p-arg69trp-in-rnaseh2c-is-a-founder-variant-in-three-indian-families-with-aicardi-gouti%C3%A3-res-syndrome
#1
Malavika Hebbar, Anil Kanthi, Aroor Shrikiran, Snehal Patil, Mamta Muranjan, Febi Francis, Vishnu Bhat B, Katta M Girisha, Anju Shukla
Aicardi-Goutières syndrome is an early-onset severe neurological disorder characterized by intracranial calcification, white matter abnormalities, hepatosplenomegaly, cerebrospinal fluid lymphocytosis, and elevated interferon-α levels, thus mimicking congenital viral infections. It is a genetically heterogeneous condition and autosomal recessive and autosomal dominant forms with variations in seven genes known till date. Variations in RNASEH2C cause an autosomal recessive form of AGS. Here we report three Indian families with variant, c...
November 17, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29150641/repurposing-of-the-anti-malaria-drug-chloroquine-for-zika-virus-treatment-and-prophylaxis
#2
Sergey A Shiryaev, Pinar Mesci, Antonella Pinto, Isabella Fernandes, Nicholas Sheets, Sujan Shresta, Chen Farhy, Chun-Teng Huang, Alex Y Strongin, Alysson R Muotri, Alexey V Terskikh
One of the major challenges of the current Zika virus (ZIKV) epidemic is to prevent congenital foetal abnormalities, including microcephaly, following ZIKV infection of pregnant women. Given the urgent need for ZIKV prophylaxis and treatment, repurposing of approved drugs appears to be a viable and immediate solution. We demonstrate that the common anti-malaria drug chloroquine (CQ) extends the lifespan of ZIKV-infected interferon signalling-deficient AG129 mice. However, the severity of ZIKV infection in these mice precludes the study of foetal (vertical) viral transmission...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150602/tlr7-mediated-viral-recognition-results-in-focal-type-i-interferon-secretion-by-dendritic-cells
#3
Shin-Ichiroh Saitoh, Fumiko Abe, Atsuo Kanno, Natsuko Tanimura, Yoshiko Mori Saitoh, Ryutaro Fukui, Takuma Shibata, Katsuaki Sato, Takeshi Ichinohe, Mayumi Hayashi, Kazuishi Kubota, Hiroko Kozuka-Hata, Masaaki Oyama, Yorifumi Kikko, Toshiaki Katada, Kenji Kontani, Kensuke Miyake
Plasmacytoid dendritic cells (pDC) sense viral RNA through toll-like receptor 7 (TLR7), form self-adhesive pDC-pDC clusters, and produce type I interferons. This cell adhesion enhances type I interferon production, but little is known about the underlying mechanisms. Here we show that MyD88-dependent TLR7 signaling activates CD11a/CD18 integrin to induce microtubule elongation. TLR7(+) lysosomes then become linked with these microtubules through the GTPase Arl8b and its effector SKIP/Plekhm2, resulting in perinuclear to peripheral relocalization of TLR7...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29150440/license-to-kill-ifn-%C3%AE-regulates-antifungal-activity-of-neutrophils
#4
REVIEW
Daniel Schnepf, Peter Staeheli
Interferon-λ mediates antifungal immunity by stimulating neutrophils to generate reactive oxygen species.
November 17, 2017: Science Immunology
https://www.readbyqxmd.com/read/29150432/the-ikk-related-kinase-tbk1-activates-mtorc1-directly-in-response-to-growth-factors-and-innate-immune-agonists
#5
Cagri Bodur, Dubek Kazyken, Kezhen Huang, Bilgen Ekim Ustunel, Kate A Siroky, Aaron Seth Tooley, Ian E Gonzalez, Daniel H Foley, Hugo A Acosta-Jaquez, Tammy M Barnes, Gabrielle K Steinl, Kae-Won Cho, Carey N Lumeng, Steven M Riddle, Martin G Myers, Diane C Fingar
The innate immune kinase TBK1 initiates inflammatory responses to combat infectious pathogens by driving production of type I interferons. TBK1 also controls metabolic processes and promotes oncogene-induced cell proliferation and survival. Here, we demonstrate that TBK1 activates mTOR complex 1 (mTORC1) directly. In cultured cells, TBK1 associates with and activates mTORC1 through site-specific mTOR phosphorylation (on S2159) in response to certain growth factor receptors (i.e., EGF-receptor but not insulin receptor) and pathogen recognition receptors (PRRs) (i...
November 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29150430/interferon-%C3%A1%C2%B5-2-signaling-in-melanocytes-and-melanoma-cells-regulates-expression-of-ctla-4
#6
Xuan Mo, Hanghang Zhang, Sarah Preston, Kayla Martin, Bo Zhou, Nish Vadalia, Ana M Gamero, Jonathan Soboloff, Italo Tempera, M Raza Zaidi
CTLA-4 is a cell surface receptor on T cells that functions as an immune checkpoint molecule to enforce tolerance to cognate antigens. Anti-CTLA-4 immunotherapy is highly effective at reactivating T cell responses against melanoma, which is postulated to be due to targeting CTLA-4 on T cells. Here we report that CTLA-4 is also highly expressed by most human melanoma cell lines, as well as in normal human melanocytes. Interferon-gamma (IFNG) signaling activated the expression of the human CTLA-4 gene in a melanocyte and melanoma cell-specific manner...
November 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/29150429/cgamp-a-tale-of-two-signals
#7
Teneema Kuriakose, Thirumala-Devi Kanneganti
In this issue of JEM, Swanson et al. (https://doi.org/10.1084/jem.20171749) report an unanticipated role for cGAMP in priming and activation of inflammasomes in addition to its well-characterized function as an endogenous second messenger inducing type I interferons in the cytosolic DNA-sensing pathway.
November 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29150375/type-i-interferon-and-proinflammatory-cytokine-levels-in-cerebrospinal-fluid-of-newborns-with-rotavirus-associated-leukoencephalopathy
#8
Kyung Yeon Lee, Chang Hoon Moon, Seong Hoon Choi
OBJECTIVE: The purpose of this study was to identify whether there is an increase in type I interferon and proinflammatory cytokine levels in the cerebrospinal fluid of newborns with rotavirus-associated leukoencephalopathy. METHODS: Levels of type I interferons (interferon-alpha and interferon-beta) and proinflammatory cytokines (interleukin-6 and interferon-gamma) were measured in the cerebrospinal fluid of 23 newborns with rotavirus-associated leukoencephalopathy (patient group) and 39 infants under 90 days-of-age (control group)...
November 14, 2017: Brain & Development
https://www.readbyqxmd.com/read/29150240/dichotomous-expression-of-tnf-superfamily-ligands-on-antigen-presenting-cells-controls-post-priming-anti-viral-cd4-t-cell-immunity
#9
Yu-Han Chang, Kuan Chung Wang, Kuan-Lun Chu, Derek L Clouthier, Anh T Tran, Miguel S Torres Perez, Angela C Zhou, Ali A Abdul-Sater, Tania H Watts
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4(+) T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found that type I interferon (IFN-I) induced TNFSF ligands GITRL, 4-1BBL, OX40L, and CD70 predominantly on monocyte-derived APCs and CD80 and CD86 predominantly on classical dendritic cells (cDCs)...
November 13, 2017: Immunity
https://www.readbyqxmd.com/read/29149822/olive-leaf-extracts-act-as-modulators-of-the-human-immune-response
#10
Thea Magrone, Anna Spagnoletta, Rosaria Salvatore, Manrico Magrone, Francesco Dentamaro, Matteo Antonio Russo, Graziana Difonzo, Carmine Summo, Francesco Caponio, Emilio Jirillo
BACKGROUND: Olive tree leaves have been used in the Mediterranean area as traditional medicine in virtue of their healthy effects. Olive leaf extracts (OLEs) contain higher amounts of polyphenols than those detected in the extra virgin olive oil and fruit. Several lines of evidence support the cardioprotective, anti-oxidant and anti-inflammatory activities exerted by OLEs. METHODS: Peripheral blood mononuclear cells (PBMCs) from twenty-five healthy donors were cultured in the presence of 3 μg of two OLE extracts, extract A (resuspended in water) and extract B (resuspended in 70% ethanol)...
November 15, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/29149781/macrophages-from-behcet-s-disease-patients-express-decreased-level-of-aryl-hydrocarbon-receptor-ahr-mrna
#11
Mohammad Taghi Palizgir, Maryam Akhtari, Mahdi Mahmoudi, Shayan Mostafaei, Alireza Rezaeimanesh, Massoomeh Akhlaghi, Farhad Shahram
Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor, connecting environmental stimulators with the immune system. M1 macrophages are a part of immune system that contribute to the inflammatory events in the pathogenesis of Behcet's disease (BD). The effect of AHR on the macrophages in BD patients is still unclear. In this study, we investigated the mRNA expression of AHR in the monocyte-derived and M1 macrophages in active BD patients in comparison to healthy controls. Isolated monocytes from 10 healthy controls and 10 active BD patients were differentiated to macrophages by macrophage-colony stimulating factor (M-CSF) for 7 days...
October 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29149056/characterization-of-ovine-a3z1-restriction-properties-against-small-ruminant-lentiviruses-srlvs
#12
Lorena de Pablo-Maiso, Idoia Glaria, Helena Crespo, Estanislao Nistal-Villán, Valgerdur Andrésdóttir, Damián de Andrés, Beatriz Amorena, Ramsés Reina
Intrinsic factors of the innate immune system include the apolipoprotein B editing enzyme catalytic polypeptide-like 3 (APOBEC3) protein family. APOBEC3 inhibits replication of different virus families by cytosine deamination of viral DNA and a not fully characterized cytosine deamination-independent mechanism. Sheep are susceptible to small ruminant lentivirus (SRLVs) infection and contain three APOBEC3 genes encoding four proteins (A3Z1, Z2, Z3 and Z2-Z3) with yet not deeply described antiviral properties...
November 17, 2017: Viruses
https://www.readbyqxmd.com/read/29147886/peromyscus-leucopus-mouse-brain-transcriptome-response-to-powassan-virus-infection
#13
Luwanika Mlera, Kimberly Meade-White, Eric Dahlstrom, Rachel Baur, Kishore Kanakabandi, Kimmo Virtaneva, Stephen F Porcella, Marshall E Bloom
Powassan virus (POWV) is a tick-borne Flavivirus responsible for life-threatening encephalitis in North America and some regions of Russia. The ticks that have been reported to transmit the virus belong to the Ixodes species, and they feed on small-to-medium-sized mammals, such as Peromyscus leucopus mice, skunks, and woodchucks. We previously developed a P. leucopus mouse model of POWV infection, and the model is characterized by a lack of clinical signs of disease following intraperitoneal or intracranial inoculation...
November 16, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/29147873/comparison-of-the-adjuvanticity-of-two-adjuvant-formulations-containing-de-o-acylated-lipooligosaccharide-on-japanese-encephalitis-vaccine-in-mice
#14
Ara Ko, Seo Ri Wui, Ji In Ryu, Hien Thi Thu Do, Yeon Jeong Lee, Soo Jeong Lim, Inmoo Rhee, Dae Im Jung, Jin-Ah Park, Jung-Ah Choi, Man Ki Song, Na Gyong Lee
Adjuvants are essential vaccine components used to enhance, accelerate, and/or prolong adaptive immunity against specific vaccine antigens. In this study, we compared the adjuvanticity of two adjuvant formulations containing de-O-acylated lipooligosaccharide (dLOS), a toll-like receptor 4 agonist, on the Japanese encephalitis (JE) vaccine in mice. Mice were immunized once or twice at a two-week interval with inactivated JE vaccine in the absence or presence of adjuvant. We found that both the alum- and the liposome-based formulation induced significantly faster and higher serum IgG antibody responses as compared with the non-adjuvanted vaccine after either one or two immunizations...
November 17, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29147645/real-world-cure-rates-for-hepatitis-c-virus-treatments-that-include-simeprevir-and-or-sofosbuvir-are-comparable-to-clinical-trial-results
#15
Kian Bichoupan, Neeta Tandon, James F Crismale, Joshua Hartman, David Del Bello, Neal Patel, Sweta Chekuri, Alyson Harty, Michel Ng, Keith M Sigel, Meena B Bansal, Priya Grewal, Charissa Y Chang, Jennifer Leong, Gene Y Im, Lawrence U Liu, Joseph A Odin, Nancy Bach, Scott L Friedman, Thomas D Schiano, Ponni V Perumalswami, Douglas T Dieterich, Andrea D Branch
AIM: To assess the real-world effectiveness and cost of simeprevir (SMV), and/or sofosbuvir (SOF)-based therapy for chronic hepatitis C virus (HCV) infection. METHODS: The real-world performance of patients treated with SMV/SOF ± ribavirin (RBV), SOF/RBV, and SOF/RBV with pegylated-interferon (PEG) were analyzed in a consecutive series of 508 patients with chronic HCV infection treated at a single academic medical center. Patients with genotypes 1 through 4 were included...
November 12, 2017: World Journal of Virology
https://www.readbyqxmd.com/read/29147627/stat1-gene-deficient-mice-develop-accelerated-breast-cancer-growth-and-metastasis-which-is-reduced-by-il-17-blockade
#16
Sanjay Varikuti, Steve Oghumu, Mohamad Elbaz, Greta Volpedo, Dinesh K Ahirwar, Pablo C Alarcon, Rachel H Sperling, Ellen Moretti, Marissa S Pioso, Jennifer Kimble, Mohd W Nasser, Ramesh K Ganju, Cesar Terrazas, Abhay R Satoskar
Signal transducer and activator of transcription 1 (STAT1) mediates interferon gamma signaling which activates the expression of various genes related to apoptosis, inflammation, cell cycle and angiogenesis. Several experimental and clinical studies have investigated the role of STAT1 in primary tumor growth in breast cancer; however, its role in tumor metastasis remains to be determined. To determine the role of STAT1 in breast cancer metastasis, we analyzed growth and metastasis in WT or STAT1(-/-) mice orthotopically implanted with metastatic 4T1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147614/exploiting-a-new-strategy-to-induce-immunogenic-cell-death-to-improve-dendritic-cell-based-vaccines-for-lymphoma-immunotherapy
#17
B Montico, C Lapenta, M Ravo, D Martorelli, E Muraro, B Zeng, E Comaro, M Spada, S Donati, S M Santini, R Tarallo, G Giurato, F Rizzo, A Weisz, F Belardelli, R Dolcetti, J Dal Col
Although promising, the clinical benefit provided by dendritic cell (DC)-based vaccines is still limited and the choice of the optimal antigen formulation is still an unresolved issue. We have developed a new DC-based vaccination protocol for aggressive and/or refractory lymphomas which combines the unique features of interferon-conditioned DC (IFN-DC) with highly immunogenic tumor cell lysates (TCL) obtained from lymphoma cells undergoing immunogenic cell death. We show that treatment of mantle cell lymphoma (MCL) and diffuse large B-cell lymphoma (DLBCL) cell lines with 9-cis-retinoic acid and IFNα (RA/IFNα) induces early membrane exposure of Calreticulin, HSP70 and 90 together with CD47 down-regulation and enhanced HMGB1 secretion...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147443/4-nitroquinoline-1-oxide-induced-tongue-and-esophagus-carcinogenesis-in-obese-and-diabetic-tsod-mice
#18
Takuji Tanaka, Kunihiro Kawabata, Shigeyuki Sugie
Background: Obesity and diabetes mellitus are associated with lifestyle-related carcinogenesis. They are also risk factors of esophageal adenocarcinoma, but there are only a few reports on association between obesity/diabetes and development of squamous cell carcinoma in the oral cavity and esophagus. In this study, we therefore aimed to determine whether obesity and diabetes affect oral and esophageal carcinogenesis using model mice of obesity and diabetes, the Tsumura Suzuki obese diabetes (TSOD) and Tsumura Suzuki non-obesity (TSNO) control mice, which were treated with 4-nitroquinoline 1-oxide (4-NQO) to produce tongue and esophageal carcinomas...
August 2017: World Journal of Oncology
https://www.readbyqxmd.com/read/29146546/signaling-via-toll-like-receptor-4-and-cd40-in-b-cells-plays-a-regulatory-role-in-the-pathogenesis-of-multiple-sclerosis-through-interleukin-10-production
#19
Yoichiro Okada, Hirofumi Ochi, Chihiro Fujii, Yuichiro Hashi, Mio Hamatani, Shinji Ashida, Kazuyuki Kawamura, Hirofumi Kusaka, Sadayuki Matsumoto, Masanori Nakagawa, Toshiki Mizuno, Ryosuke Takahashi, Takayuki Kondo
BACKGROUND: B cells play an important role in the development of multiple sclerosis (MS), but can also exhibit regulatory functions through IL-10 production. Toll-like receptors (TLR) and CD40 signaling are likely to be involved in this process. OBJECTIVE: To investigate the ability of MS B cells to produce IL-10 in response to TLR stimulation in the presence or absence of CD40 co-stimulation. METHODS: Peripheral blood mononuclear cells obtained from 34 MS patients and 24 matched healthy participants (HS) were stimulated through either TLR4 or TLR9 alone, or together with CD40...
November 13, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29146236/infectious-bursal-disease-virus-protein-vp4-suppresses-type-i-interferon-expression-via-inhibiting-k48-linked-ubiquitylation-of-glucocorticoid-induced-leucine-zipper-gilz
#20
Zhiyuan He, Xiang Chen, Mengjiao Fu, Jun Tang, Xiaoqi Li, Hong Cao, Yongqiang Wang, Shijun J Zheng
Viruses have developed a variety of methods to evade host immune response. Our previous study showed that infectious bursal disease virus (IBDV) inhibited type I interferon production via interaction of VP4 with cellular glucocorticoid-induced leucine zipper (GILZ) protein. However, the exact underlying molecular mechanism is still unclear. In this study, we found that IBDV VP4 suppressed GILZ degradation by inhibiting K48-linked ubiquitylation of GILZ. Furthermore, mutation of VP4 (R41G) abolished the inhibitory effect of VP4 on IFN-β expression and GILZ ubiquitylation, indicating that the amino acid 41R of VP4 was required for the suppression of IFN-β expression and GILZ ubiquitylation...
October 28, 2017: Immunobiology
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