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Interferon type I immunity

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https://read.qxmd.com/read/30775439/ndr2-promotes-the-antiviral-immune-response-via-facilitating-trim25-mediated-rig-i-activation-in-macrophages
#1
Zhiyong Liu, Cheng Wu, Yueyun Pan, Huan Liu, Xiumei Wang, Yuting Yang, Meidi Gu, Yuanyuan Zhang, Xiaojian Wang
Retinoic acid-inducible gene I (RIG-I), a pivotal cytosolic sensor, recognizes viral RNAs to initiate antiviral innate immunity. However, posttranslational regulation of RIG-I signaling is not well understood. We report here that nuclear Dbf2-related kinase 2 (NDR2) functions as a crucial positive regulator of the RIG-I-mediated antiviral immune response. Overexpression of NDR2 or its kinase-inactive mutants potentiates RNA virus-induced production of type I interferons and proinflammatory cytokines and dampens viral replication...
February 2019: Science Advances
https://read.qxmd.com/read/30772497/sting-associated-lung-disease-in-mice-relies-on-t-cells-but-not-type-i-interferon
#2
Hella Luksch, W Alexander Stinson, Derek J Platt, Wei Qian, Gowri Kalugotla, Cathrine A Miner, Brock G Bennion, Alexander Gerbaulet, Angela Rösen-Wolff, Jonathan J Miner
BACKGROUND: Monogenic interferonopathies are thought to be mediated by type I interferon (IFN). For example, a gain-of-function mutation in STING (STING N153S) up-regulates type I IFN-stimulated genes (ISGs) and causes perivascular inflammatory lung disease in mice. The equivalent mutation in humans also causes lung disease, which is thought to require signaling through the cGAS-STING pathway and subsequent activation of IFN regulatory factors (IRF) 3/7, type I IFN, and ISGs. OBJECTIVE: We set out to define the roles of cGAS, IRF3, IRF7, the type I IFN receptor (IFNAR1), T cells, and B cells in spontaneous lung disease in STING N153S mice...
February 14, 2019: Journal of Allergy and Clinical Immunology
https://read.qxmd.com/read/30770713/innate-immunity-and-interferons-in-the-pathogenesis-of-sj%C3%A3-gren-s-syndrome
#3
Iris L A Bodewes, Albin Björk, Marjan A Versnel, Marie Wahren-Herlenius
Primary SS (pSS) is a rheumatic disease characterized by an immune-mediated exocrinopathy, resulting in severe dryness of eyes and mouth. Systemic symptoms include fatigue and joint pain and a subset of patients develop more severe disease with multi-organ involvement. Accumulating evidence points to involvement of innate immunity and aberrant activity of the type I IFN system in both the initiation and propagation of this disease. Analysis of the activity of IFN-inducible genes has evidenced that more than half of pSS patients present with a so-called 'type I IFN signature'...
February 15, 2019: Rheumatology
https://read.qxmd.com/read/30770349/atr-inhibition-potentiates-the-radiation-induced-inflammatory-tumour-microenvironment
#4
Magnus T Dillon, Katharina F Bergerhoff, Malin Pedersen, Emmanuel C Patin, Harriet Whittock, Eva Crespo-Rodriguez, Alex Pearson, James T Paget, Henry G Smith, Radhika R Patel, Shane Foo, Galabina Bozhanova, Chanthirika Ragulan, Elisa Fontana, Krisha Desai, Anna C Wilkins, Anguraj Sadanandam, Alan Melcher, Martin McLaughlin, Kevin J Harrington
PURPOSE: ATR inhibitors (ATRi) are in early phase clinical trials and have been shown to sensitise to chemotherapy and radiotherapy preclinically. No data have been published about the effect of these drugs on the tumor microenvironment. EXPERIMENTAL DESIGN: We used an immunocompetent mouse model of HPV-driven malignancies to investigate the ATR inhibitor AZD6738 in combination with fractionated radiation (RT). Gene expression analysis and flow cytometry were performed post-therapy...
February 15, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://read.qxmd.com/read/30769920/tho-complex-subunit-7-homolog-negatively-regulates-cellular-antiviral-response-against-rna-viruses-by-targeting-tbk1
#5
Tian-Sheng He, Tao Xie, Jing Li, Ya-Xian Yang, Changsheng Li, Weiying Wang, Lingzhen Cao, Hua Rao, Cynthia Ju, Liang-Guo Xu
RNA virus invasion induces a cytosolic RIG-I-like receptor (RLR) signaling pathway by promoting assembly of the Mitochondrial antiviral-signaling protein (MAVS) signalosome and triggers the rapid production of type I interferons (IFNs) and proinflammatory cytokines. During this process, the pivotal kinase TANK binding kinase 1 (TBK1) is recruited to the MAVS signalosome to transduce a robust innate antiviral immune response by phosphorylating transcription factors interferon regulatory factor 3 (IRF3) and nuclear factor (NF)-κB and promoting their nuclear translocation...
February 15, 2019: Viruses
https://read.qxmd.com/read/30762199/manipulating-the-interferon-signaling-pathway-implications-for-hiv-infection
#6
REVIEW
Krystelle Nganou-Makamdop, Daniel C Douek
During human immunodeficiency virus (HIV) infection, type I interferon (IFN-I) signaling induces an antiviral state that includes the production of restriction factors that inhibit virus replication, thereby limiting the infection. As seen in other viral infections, type I IFN can also increase systemic immune activation which, in HIV disease, is one of the strongest predictors of disease progression to acquired immune deficiency syndrome (AIDS) and non-AIDS morbidity and mortality. Moreover, IFN-I is associated with CD4 T cell depletion and attenuation of antigen-specific T cell responses...
February 14, 2019: Virologica Sinica
https://read.qxmd.com/read/30761127/p31-43-gliadin-peptide-forms-oligomers-and-induces-nlrp3-inflammasome-caspase-1-dependent-mucosal-damage-in-small-intestine
#7
María Florencia Gómez Castro, Emanuel Miculán, María Georgina Herrera, Carolina Ruera, Federico Perez, Eduardo Daniel Prieto, Exequiel Barrera, Sergio Pantano, Paula Carasi, Fernando Gabriel Chirdo
Celiac disease (CD) is a chronic enteropathy elicited by a Th1 response to gluten peptides in the small intestine of genetically susceptible individuals. However, it remains unclear what drives the induction of inflammatory responses of this kind against harmless antigens in food. In a recent work, we have shown that the p31-43 peptide (p31-43) from α-gliadin can induce an innate immune response in the intestine and that this may initiate pathological adaptive immunity. The receptors and mechanisms responsible for the induction of innate immunity by p31-43 are unknown and here we present evidence that this may reflect conformational changes in the peptide that allow it to activate the NLRP3 inflammasome...
2019: Frontiers in Immunology
https://read.qxmd.com/read/30761126/ethyl-pyruvate-modulates-murine-dendritic-cell-activation-and-survival-through-their-immunometabolism
#8
Marita Chakhtoura, Robert W Chain, Priscila Y Sato, Connie C Qiu, Michael H Lee, Joseph J Meissler, Toby K Eisenstein, Walter J Koch, Roberto Caricchio, Stefania Gallucci
Attenuating the innate immunity activation could ameliorate inflammation and disease in settings such as transplant rejection or autoimmunity. Recently, a pivotal role for metabolic re-programming in TLR-induced dendritic cell (DC) activation has emerged. Ethyl pyruvate (EP), a pyruvate derivative, possesses anti-inflammatory properties in vitro and in animal models of disease. However, its effects on DCs remain elusive. We found that EP attenuated LPS-induced activation of murine GM-CSF bone marrow-derived dendritic cells (DCs) in vitro , reducing pro-inflammatory cytokine and IL-10 production, costimulatory molecule and MHC expression, the type I Interferon (IFN-I) response, the LPS-induced cell death, and the ability of DCs to stimulate allogeneic T cells...
2019: Frontiers in Immunology
https://read.qxmd.com/read/30761124/cytokine-targeting-by-mirnas-in-autoimmune-diseases
#9
REVIEW
Valentina Salvi, Veronica Gianello, Laura Tiberio, Silvano Sozzani, Daniela Bosisio
Persistent and excessive cytokine production is a hallmark of autoimmune diseases and may play a role in disease pathogenesis and amplification. Therefore, cytokine neutralization is a useful therapeutic strategy to treat immune-mediated conditions. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression in diverse biological processes. Altered miRNA levels are observed in most autoimmune diseases and are recognized to influence autoimmunity through different mechanisms. Here, we review the impact of altered miRNA levels on the expression of cytokines that play a relevant pathogenic role in autoimmunity, namely primary pro-inflammatory cytokines, the IL-17/IL-23 axis, type I interferons and IL-10...
2019: Frontiers in Immunology
https://read.qxmd.com/read/30760614/dose-dependent-differences-in-hiv-inhibition-by-different-interferon-alpha-subtypes-while-having-overall-similar-biologic-effects
#10
Erika Schlaepfer, Audrey Fahrny, Maarja Gruenbach, Stefan P Kuster, Viviana Simon, Gideon Schreiber, Roberto F Speck
Type I interferons (IFNs) are key players in the antiviral immune response. Interferon alpha (IFN-α) belongs to this class of IFNs and comprises 12 subtypes that differ from each other in their binding affinities for a common receptor and, thus, in their signaling potencies. Recent data suggest that IFN-α6 and -α14 are the most potent IFN-α subtypes in restricting HIV replication when applied exogenously. However, in the context of antiviral therapy, IFNs are administered at high doses, which may compensate for differences in potency seen between IFN-α subtypes...
February 13, 2019: MSphere
https://read.qxmd.com/read/30755715/niraparib-activates-interferon-signaling-and-potentiates-anti-pd-1-antibody-efficacy-in-tumor-models
#11
Zebin Wang, Kaiming Sun, Yonghong Xiao, Bin Feng, Keith Mikule, XiaoYan Ma, Ningping Feng, Christopher P Vellano, Lorenzo Federico, Joseph R Marszalek, Gordon B Mills, Jeffrey Hanke, Sridhar Ramaswamy, Jing Wang
PARP inhibitors have been proven clinically efficacious in platinum-responsive ovarian cancer regardless of BRCA1/2 status and in breast cancers with germline BRCA1/2 mutation. However, resistance to PARP inhibitors may preexist or evolve during treatment in many cancer types and may be overcome by combining PARP inhibitors with other therapies, such as immune checkpoint inhibitors, which confer durable responses and are rapidly becoming the standard of care for multiple tumor types. This study investigated the therapeutic potential of combining niraparib, a highly selective PARP1/2 inhibitor, with anti-PD-1 immune checkpoint inhibitors in preclinical tumor models...
February 12, 2019: Scientific Reports
https://read.qxmd.com/read/30755516/hiv-1-is-a-poor-inducer-of-innate-immune-responses
#12
Oya Cingöz, Stephen P Goff
Effective host immune responses against viral infection rely on the detection of the virus, activation of downstream signaling pathways, and the secretion of interferons (IFNs) and other cytokines. Many viruses can potently stimulate these responses, whereas the immune response against human immunodeficiency virus type 1 (HIV-1) remains relatively less well characterized. Here we show that HIV-1 infection with reporter viruses does not activate sensing pathways in cell lines and primary cells that are otherwise responsive to foreign nucleic acids...
February 12, 2019: MBio
https://read.qxmd.com/read/30755509/human-cytomegalovirus-immediate-early-86-kda-protein-blocks-transcription-and-induces-degradation-of-the-immature-interleukin-1%C3%AE-protein-during-virion-mediated-activation-of-the-aim2-inflammasome
#13
Sara Botto, Jinu Abraham, Nobuyo Mizuno, Kara Pryke, Bryan Gall, Igor Landais, Daniel N Streblow, Klaus J Fruh, Victor R DeFilippis
Secretion of interleukin-1β (IL-1β) represents a fundamental innate immune response to microbial infection that, at the molecular level, occurs following activation of proteolytic caspases that cleave the immature protein into a secretable form. Human cytomegalovirus (HCMV) is the archetypal betaherpesvirus that is invariably capable of lifelong infection through the activity of numerous virally encoded immune evasion phenotypes. Innate immune pathways responsive to cytoplasmic double-stranded DNA (dsDNA) are known to be activated in response to contact between HCMV and host cells...
February 12, 2019: MBio
https://read.qxmd.com/read/30753916/salmonella-spv-locus-affects-type-i-interferon-response-and-the-chemotaxis-of-neutrophils-via-suppressing-autophagy
#14
Lidan Wang, Yangli Li, Yuanhui Liu, Lingli Zuo, Yuanyuan Li, Shuyan Wu, Rui Huang
Salmonella is a facultative intracellular pathogen that can cause significant morbidity and mortality in humans and animals. Salmonella plasmid virulence (spv) gene sequence is a highly conserved 6.8 kb region which exists in the plasmid of most pathogenic Salmonella. Autophagy is a degradation process of unnecessary and dysfunctional cytoplasm components to maintain cellular homeostasis, which could affect host inflammatory responses, such as type I interferon response. Type I interferon response can promote the antibacterial activity of macrophage as well as the secretion of cytokines and neutrophil chemokines...
February 9, 2019: Fish & Shellfish Immunology
https://read.qxmd.com/read/30753544/metformin-alters-human-host-responses-to-mycobacterium-tuberculosis-in-healthy-subjects
#15
Ekta Lachmandas, Clare Eckold, Julia Böhme, Valerie A C M Koeken, Mardiana Binte Marzuki, Bastiaan Blok, Rob J W Arts, Jinmiao Chen, Karen W W Teng, Jacqueline Ratter, Elise J Smolders, Corina van den Heuvel, Rinke Stienstra, Hazel M Dockrell, Evan Newell, Mihai G Netea, Amit Singhal, Jacqueline M Cliff, Reinout van Crevel
Background: Metformin, the most widely administered diabetes drug, has been proposed as a candidate adjunctive host-directed therapy for tuberculosis, but little is known about its effects on human host responses to Mycobacterium tuberculosis. Methods: We investigated in-vitro and in-vivo effects of metformin in humans. Results: Metformin added to peripheral blood mononuclear cells from healthy volunteers enhanced in-vitro cellular metabolism whilst inhibiting the mammalian target of rapamycin (mTOR) targets p70S6K and 4EBP1, with decreased cytokine production and cellular proliferation, and increased phagocytosis...
February 12, 2019: Journal of Infectious Diseases
https://read.qxmd.com/read/30753318/type-i-interferon-protects-neurons-from-prions-in-in-vivo-models
#16
Daisuke Ishibashi, Takujiro Homma, Takehiro Nakagaki, Takayuki Fuse, Kazunori Sano, Katsuya Satoh, Tsuyoshi Mori, Ryuichiro Atarashi, Noriyuki Nishida
Infectious prions comprising abnormal prion protein, which is produced by structural conversion of normal prion protein, are responsible for transmissible spongiform encephalopathies including Creutzfeldt-Jakob disease in humans. Prions are infectious agents that do not possess a genome and the pathogenic protein was not thought to evoke any immune response. Although we previously reported that interferon regulatory factor 3 (IRF3) was likely to be involved in the pathogenesis of prion diseases, suggesting the protective role of host innate immune responses mediated by IRF3 signalling, this remained to be clarified...
February 7, 2019: Brain: a Journal of Neurology
https://read.qxmd.com/read/30753167/spatially-distinct-tumor-immune-microenvironments-stratify-triple-negative-breast-cancers
#17
Tina Gruosso, Mathieu Gigoux, Venkata Satya Kumar Manem, Nicholas Bertos, Dongmei Zuo, Irina Perlitch, Sadiq Mehdi Ismail Saleh, Hong Zhao, Margarita Souleimanova, Radia Marie Johnson, Anne Monette, Valentina Munoz Ramos, Michael Trevor Hallett, John Stagg, Réjean Lapointe, Atilla Omeroglu, Sarkis Meterissian, Laurence Buisseret, Gert Van den Eynden, Roberto Salgado, Marie-Christine Guiot, Benjamin Haibe-Kains, Morag Park
Understanding the tumor immune microenvironment (TIME) promises to be key for optimal cancer therapy, especially in triple-negative breast cancer (TNBC). Integrating spatial resolution of immune cells with laser capture microdissection gene expression profiles, we defined distinct TIME stratification in TNBC with implications for current therapies, including immune checkpoint blockade. TNBCs with an immunoreactive microenvironment exhibited tumoral infiltration of granzyme B+ CD8+ T cells, a type I interferon signature, elevated expression of multiple immune inhibitory molecules, including IDO, PD-L1, and good outcome...
February 12, 2019: Journal of Clinical Investigation
https://read.qxmd.com/read/30723081/human-megakaryocytes-possess-intrinsic-anti-viral-immunity-through-regulated-induction-of-ifitm3
#18
Robert A Campbell, Hansjorg Schwertz, Eugenio D Hottz, Jesse W Rowley, Bhanu Kanth Manne, A Valance Washington, Robert Hunter-Mellado, Neal D Tolley, Miles Christensen, Alicia S Eustes, Emilie Montenont, Seema Bhatlekar, Cassandra H Ventrone, Beth D Kirkpatrick, Kristen K Pierce, Stephen S Whitehead, Sean A Diehl, Paul F Bray, Guy A Zimmerman, Yasuhiro Kosaka, Patricia T Bozza, Fernando A Bozza, Andrew S Weyrich, Matthew T Rondina
Evolving evidence indicates that platelets and megakaryocytes (MKs) have unexpected activities in inflammation and infection; but whether viral infections upregulate biologically active, anti-viral immune genes in platelets and MKs is unknown. We examined anti-viral immune genes in these cells in dengue and influenza infections, viruses that are global public health threats. Using complementary biochemical, pharmacological, and genetic approaches, we examined the regulation and function of interferon induced transmembrane protein 3 (IFITM3), an anti-viral immune effector gene not previously studied in human platelets and MKs...
February 5, 2019: Blood
https://read.qxmd.com/read/30720117/expression-of-protein-disulfide-isomerase-a3-and-its-clinicopathological-association-in-gastric-cancer
#19
Tomohiro Shimoda, Ryuichi Wada, Shoko Kure, Kousuke Ishino, Mitsuhiro Kudo, Ryuji Ohashi, Itsuo Fujita, Eiji Uchida, Hiroshi Yoshida, Zenya Naito
Protein disulfide isomerase A3 (PDIA3) is a chaperone protein that supports the folding and processing of synthesized proteins. Its expression is associated with the prognosis of laryngeal cancer, hepatocellular carcinoma, diffuse glioma and uterine cervical cancer. In the present study, the expression levels of PDIA3 and its clinicopathological association were examined in 52 cases of gastric cancer (GC). The expression of PDIA3 was examined by immunohistochemistry and scored using a semi-quantitative method...
February 5, 2019: Oncology Reports
https://read.qxmd.com/read/30719168/multi-omics-perspective-on-the-tumor-microenvironment-based-on-pd-l1-and-cd8-t-cell-infiltration-in-urothelial-cancer
#20
Siteng Chen, Ning Zhang, Jialiang Shao, Tao Wang, Xiang Wang
Objectives: We carried out an integrated analysis based on multiple-dimensional types of data from cohorts of bladder cancer patients to identify multi-omics perspective (genomics and transcriptomics) on the tumor microenvironment on the bases of the programmed cell death 1 ligand (PD-L1) and CD8 T-cell infiltration in urothelial carcinoma. Methods: Multiple-dimensional types of data, including clinical, genomic and transcriptomic data of 408 bladder cancer patients were retrieved from the Cancer Genome Atlas database...
2019: Journal of Cancer
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