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Angela Ceribelli, Natasa Isailovic, Maria De Santis, Elena Generali, Micaela Fredi, Ilaria Cavazzana, Franco Franceschini, Luca Cantarini, Minoru Satoh, Carlo Selmi
This study aims to characterize myositis-specific antibodies in a well-defined cohort of patients with idiopathic inflammatory myopathy and to determine their association with cancer. Sera from 40 patients with polymyositis, dermatomyositis, and controls were tested by protein and RNA immunoprecipitation to detect autoantibodies, and immunoprecipitation-Western blot was used for anti-MJ/NXP-2, anti-MDA5, and anti-TIF1γ/α identification. Medical records were re-evaluated with specific focus on cancer. Anti-MJ/NXP-2 and anti-TIF1γ/α were the most common antibodies in dermatomyositis...
October 20, 2016: Clinical Rheumatology
Stefanie Luecke, Søren R Paludan
Nucleic acids sensors of the innate immune system recognize various RNA and DNA structures during infection to induce transcription of interferon and pro-inflammatory cytokines and activation of inflammasomes. Cytosolic RNA is recognized by RIG-I and MDA5, while intracellular DNA is sensed among others by cGAS, AIM2, IFI16 and RNA polymerase III. The diversity of nucleic acid species produced during infection in the cytosol and nucleus and the limited chemical differences between self and non-self nucleic acids challenge the host's innate pattern recognition system to ensure reliable sensing while avoiding immune activation by self nucleic acids...
October 14, 2016: Cytokine
Akihiko Komuro, Yuya Homma, Takaharu Negoro, Glen N Barber, Curt M Horvath
LGP2 and MDA5 cooperate to detect viral RNA in the cytoplasm of Picornavirus-infected cells and activate innate immune responses. To further define regulatory components of RNA recognition by LGP2/MDA5, a yeast two-hybrid screen was used to identify LGP2-interacting proteins. The screening has identified the TAR-RNA binding protein (TRBP), which is known to be an essential factor for RNA interference (RNAi). Immuno-precipitation experiments demonstrated that TRBP interacted specifically with LGP2 but not with related RIG-I-like receptors, RIG-I or MDA5...
October 12, 2016: Biochemical and Biophysical Research Communications
Diana M Giraldo, Juan C Hernandez, Silvio Urcuqui-Inchima
Neutrophils are key effector cells of the innate immune system and are involved in the host defense against invading pathogens such as viruses. Recently, it was reported that HIV-1-neutrophil interaction triggers neutrophil activation and promotes expression of Toll-like receptors (TLRs). Here, we assessed the role of single-stranded RNA40 (ssRNA40) derived from HIV-1 in neutrophil activation. We observed functional activation of neutrophils in response to HIV-1-derived ssRNA40 based on the expression of TLR7/8, RIG-I, and MDA5, induction of cytokines (IL-6 and TNF-α), and the production of reactive oxygen species (ROS)...
October 7, 2016: Immunologic Research
Naomi I Maria, Eline C Steenwijk, Arne S IJpma, Cornelia G van Helden-Meeuwsen, Petra Vogelsang, Wouter Beumer, Zana Brkic, Paul L A van Daele, P Martin van Hagen, Peter J van der Spek, Hemmo A Drexhage, Marjan A Versnel
OBJECTIVE: The interferon (IFN) type I signature is present in over half of patients with primary Sjögren's syndrome (pSS) and associated with higher disease-activity and autoantibody presence. Plasmacytoid dendritic cells (pDCs) are considered as the main source of enhanced IFN type I expression. The objective of this study was to unravel the molecular pathways underlying IFN type I bioactivity in pDCs of patients with pSS. METHODS: Blood samples from 42 healthy controls (HC) and 115 patients with pSS were stratified according to their IFN type I signature...
September 26, 2016: Annals of the Rheumatic Diseases
Tadaatsu Imaizumi, Chikashi Yano, Akiko Numata, Koji Tsugawa, Ryo Hayakari, Tomoh Matsumiya, Hidemi Yoshida, Shojiro Watanabe, Kazushi Tsuruga, Shogo Kawaguchi, Manabu Murakami, Hiroshi Tanaka
BACKGROUND/AIMS: Activation of Toll-like receptor 3 (TLR3) signaling followed by type I interferon (IFN) expression is crucial in antiviral and "pseudoviral" immune reactions in renal mesangial cells (MCs). These reactions are probably involved in the pathogenesis of chronic kidney disease (CKD). However, the role of IFN-induced 35-kDa protein 35 (IFI35), a type I IFN-dependent transcript, in glomerular inflammation is unclear. Here, we aimed to investigate the expression and the role of IFI35 in IFN-β/retinoic acid-inducible gene-I (RIG-I)/CCL5 and IFN-β/melanoma differentiation-associated gene 5 (MDA5)/CXCL10 axes in MCs...
September 17, 2016: Kidney & Blood Pressure Research
Jingjing Han, Yanjin Wang, Qing Chu, Tianjun Xu
The laboratory of genetics and physiology 2 (LGP2) is a member of retinoic acid-inducible gene I (RIG-I)-like receptors (RLR receptors), which may participate in the immune regulation process. The role of LGP2 on modulating signaling was ambiguous, some researchers suggested that the regulation mechanism of LGP2 to melanoma differentiation-associated gene 5 (MDA5) and retinoic acid inducible gene-I (RIG-I) were different. In this study, the bioinformatics and functions of LGP2 from miiuy croaker (mmLGP2) were characterized...
September 13, 2016: Fish & Shellfish Immunology
Ling Xu, Dandan Yu, Yu Fan, Li Peng, Yong Wu, Yong-Gang Yao
The function of the RIG-I-like receptors (RLRs; including RIG-I, MDA5, and LGP2) as key cytoplasmic sensors of viral pathogen-associated molecular patterns (PAMPs) has been subjected to numerous pathogenic challenges and has undergone a dynamic evolution. We found evolutionary evidence that RIG-I was lost in the Chinese tree shrew lineage. Along with the loss of RIG-I, both MDA5 (tMDA5) and LGP2 (tLGP2) have undergone strong positive selection in the tree shrew. tMDA5 or tMDA5/tLGP2 could sense Sendai virus (an RNA virus posed as a RIG-I agonist) for inducing type I IFN, although conventional RIG-I and MDA5 were thought to recognize distinct RNA structures and viruses...
September 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
Ana L C Valadão, Renato S Aguiar, Luciana B de Arruda
The Flaviviridae family comprises several human pathogens, including Dengue, Zika, Yellow Fever, West Nile, Japanese Encephalitis viruses, and Hepatitis C Virus. Those are enveloped, single-stranded positive sense RNA viruses, which replicate mostly in intracellular compartments associated to endoplasmic reticulum (ER) and Golgi complex. Virus replication results in abundant viral RNAs and proteins, which are recognized by cellular mechanisms evolved to prevent virus infection, resulting in inflammation and stress responses...
2016: Frontiers in Microbiology
Satoshi Sato, Yoji Uejima, Meika Nanbu, Eisuke Suganuma, Tadamasa Takano, Risa Tanaka, Tomoyuki Kabuki, Eiji Oguma, Tsutomu Oh-Ishi, Yutaka Kawano
OBJECTIVES: The aim of this study was to determine the clinical phenotype and outcome of interstitial lung disease (ILD) complicated with juvenile dermatomyositis (JDM) or juvenile polymyositis (JPM). METHODS: This was a single-center retrospective study. From 1984 to 2015, we retrospectively reviewed 29 patients who were diagnosed with JDM/JPM, among whom eight cases were ILD and 21 were non-ILD. The clinical features and laboratory findings included chest computed tomography (CT) images that were compared between the patients with ILD and non-ILD...
September 20, 2016: Modern Rheumatology
Xiaofeng Sun, Liwei Sun, Yuanyuan Zhao, Ying Li, Wei Lin, Dahua Chen, Qinmiao Sun
Mitochondrial antiviral signalling protein (MAVS) acts as a critical adaptor protein to transduce antiviral signalling by physically interacting with activated RIG-I and MDA5 receptors. MAVS executes its functions at the outer membrane of mitochondria to regulate downstream antiviral signalling, indicating that the mitochondria provides a functional platform for innate antiviral signalling transduction. However, little is known about whether and how MAVS-mediated antiviral signalling contributes to mitochondrial homeostasis...
2016: Cell Discovery
Seung-No Hong, Ji Young Kim, Hanna Kim, Dong-Young Kim, Tae-Bin Won, Doo Hee Han, Chae-Seo Rhee, Hyun Jik Kim
The innate immune response, which constitutes the first line of defense against influenza A virus (IAV) infection, is activated by pattern recognition receptors (PRRs) that recognize viral structures. We found that the PRRs, retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), which have been implicated as interferon (IFN)-stimulated genes, were dominantly responsible for the recognition of IAV in lungs of mice at 3 and 7 days post infection (dpi). Intranasal administration of IFNs enhanced RIG-I and MDA5 gene expression after IAV infection and mRNA levels of RIG-I and MDA5 were significantly reduced at 7 dpi in mice with neutralization of secreted IFNs...
October 2016: Antiviral Research
Ying Yang, Youhua Huang, Yepin Yu, Sheng Zhou, Shaowen Wang, Min Yang, Qiwei Qin, Xiaohong Huang
Increased reports uncovered that mammalian tripartite motif-containing 62 (TRIM62) exerts crucial roles in cancer and innate immune response. However, the roles of fish TRIM62 in antiviral immune response remained uncertain. In this study, a TRIM62 gene was cloned from orange spotted grouper (EcTRIM62) and its roles in grouper RNA virus infection was elucidated in vitro. EcTRIM62 shared 99% and 83% identity to bicolor damselfish (Stegastes partitus) and human (Homo sapiens), respectively. Sequence alignment indicated that EcTRIM62 contained three domains, including a RING-finger domain, a B-box domain and a SPRY domain...
October 2016: Fish & Shellfish Immunology
Olivier Benveniste, Werner Stenzel, Yves Allenbach
PURPOSE OF REVIEW: Inflammatory myopathies are rare diseases. Their diagnosis criteria are historically based on their clinical phenotype (topography of the muscle weakness, presence of skin lesions and/or of extra-skin/muscle signs) and the presence of inflammatory infiltrates on muscle biopsy. However, the recent discovery of different myositis-specific antibodies (MSA) or myositis-associated antibodies (MAA) permitted to revisit these old classifications. This review covers recent findings in clinical and pathological phenotypes regarding prognosis, associated cancer and response to the treatment based on MSA/MAA categorization...
October 2016: Current Opinion in Neurology
Manabu Fujimoto, Rei Watanabe, Yosuke Ishitsuka, Naoko Okiyama
PURPOSE OF REVIEW: In dermatomyositis, disease-specific autoantibodies now cover more than 70% of patients. These autoantibodies closely correlate with distinct clinical manifestations. In the past few years, extensive evidence has been accumulated on clinical significance of dermatomyositis-specific autoantibodies including autoantibodies against melanoma differentiation antigen 5 (MDA5), transcriptional intermediary factor 1 (TIF1), nuclear matrix protein 2 (NXP2), and small ubiquitin-like modifier activating enzyme (SAE)...
November 2016: Current Opinion in Rheumatology
Haruka Chino, Akimasa Sekine, Tomohisa Baba, Tae Iwasawa, Koji Okudela, Tamiko Takemura, Harumi Itoh, Shinji Sato, Yasuo Suzuki, Takashi Ogura
We herein present the first case of rapidly progressive interstitial lung disease (RP-ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody evaluated by surgical lung biopsy (SLB). High-resolution CT scan revealed perilobular opacities, which rapidly became thicker and formed consolidation, resulting in remarkable loss of lung volume. Specimens taken from SLB revealed membranous organization with alveolar occlusion, dilation of alveolar ducts, and sacs with collapsed alveoli, which are typical features of diffuse alveolar damage (DAD)...
2016: Internal Medicine
Maria Pujantell, Roger Badia, Cristina Ramirez, Teresa Puig, Bonaventura Clotet, Ester Ballana, José A Esté, Eva Riveira-Muñoz
HIV-1 infection is thought to impair type I interferon (IFN-I) production in macrophages, a cell type that is also relatively resistant to HIV-1 cytotoxic effects. Here, we show that monocyte differentiation into macrophages by M-CSF led to cell proliferation and susceptibility to HIV-1 infection that induced cell cycle arrest and increased cell death. Established HIV-1 infection of monocyte-derived macrophages induced the upregulation of the pattern recognition receptors MDA5 and Rig-I that serve as virus sensors; production of interferon-β, and transcription of interferon-stimulated genes including CXCL10...
September 2016: Antiviral Research
T Matsushita, K Mizumaki, M Kano, N Yagi, M Tennichi, A Takeuchi, Y Okamoto, Y O Hamaguchi, A Murakami, M Hasegawa, M Kuwana, M Fujimoto, K Takehara
BACKGROUND: Anti-MDA5 antibodies are associated with rapidly progressive interstitial lung disease (RP-ILD) in patients with clinically amyopathic dermatomyositis (CADM) or dermatomyositis (DM). OBJECTIVE: We aimed to evaluate the relevance of monitoring anti-MDA5 antibody levels for the management of RP-ILD in patients with CADM or DM. METHODS: Twelve patients with CADM or DM (CADM, 10; DM, 2) accompanied by RP-ILD were included. Baseline characteristics and outcomes were recorded...
July 25, 2016: British Journal of Dermatology
Shilong Chen, Guifeng Luo, Zhou Yang, Shuncheng Lin, Shaoying Chen, Song Wang, Mohsan Ullah Goraya, Xiaojuan Chi, Xiancheng Zeng, Ji-Long Chen
Avian Tembusu virus (ATMUV) is a newly emerged flavivirus that belongs to the Ntaya virus group. ATMUV is a highly pathogenic virus causing significant economic loss to the Chinese poultry industry. However, little is known about the role of host innate immune mechanism in defending against ATMUV infection. In this study, we found that ATMUV infection significantly up-regulated the expression of type I and type III interferons (IFN) and some critical IFN-stimulated genes (ISG) in vivo and in vitro. This innate immune response was induced by genomic RNA of ATMUV...
2016: Veterinary Research
Matheswaran Kandasamy, Amol Suryawanshi, Smanla Tundup, Jasmine T Perez, Mirco Schmolke, Santhakumar Manicassamy, Balaji Manicassamy
Retinoic acid inducible gene-I (RIG-I) is an innate RNA sensor that recognizes the influenza A virus (IAV) RNA genome and activates antiviral host responses. Here, we demonstrate that RIG-I signaling plays a crucial role in restricting IAV tropism and regulating host immune responses. Mice deficient in the RIG-I-MAVS pathway show defects in migratory dendritic cell (DC) activation, viral antigen presentation, and priming of CD8+ and CD4+ T cell responses during IAV infection. These defects result in decreased frequency of polyfunctional effector T cells and lowered protection against heterologous IAV challenge...
July 2016: PLoS Pathogens
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