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mitochondrial immunity

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https://www.readbyqxmd.com/read/28819133/combined-transcriptome-and-metabolome-analyses-of-metformin-effects-reveal-novel-links-between-metabolic-networks-in-steroidogenic-systems
#1
Sameer S Udhane, Balazs Legeza, Nesa Marti, Damian Hertig, Gaëlle Diserens, Jean-Marc Nuoffer, Peter Vermathen, Christa E Flück
Metformin is an antidiabetic drug, which inhibits mitochondrial respiratory-chain-complex I and thereby seems to affect the cellular metabolism in many ways. It is also used for the treatment of the polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. In addition, metformin possesses antineoplastic properties. Although metformin promotes insulin-sensitivity and ameliorates reproductive abnormalities in PCOS, its exact mechanisms of action remain elusive. Therefore, we studied the transcriptome and the metabolome of metformin in human adrenal H295R cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818792/regulation-of-type-i-interferon-responses-by-mitochondria-derived-reactive-oxygen-species-in-plasmacytoid-dendritic-cells
#2
Zsofia Agod, Tünde Fekete, Marietta M Budai, Aliz Varga, Attila Szabo, Hyelim Moon, Istvan Boldogh, Tamas Biro, Arpad Lanyi, Attila Bacsi, Kitti Pazmandi
Mitochondrial reactive oxygen species (mtROS) generated continuously under physiological conditions have recently emerged as critical players in the regulation of immune signaling pathways. In this study we have investigated the regulation of antiviral signaling by increased mtROS production in plasmacytoid dendritic cells (pDCs), which, as major producers of type I interferons (IFN), are the key coordinators of antiviral immunity. The early phase of type I IFN production in pDCs is mediated by endosomal Toll-like receptors (TLRs), whereas the late phase of IFN response can also be triggered by cytosolic retinoic acid-inducible gene-I (RIG-I), expression of which is induced upon TLR stimulation...
July 29, 2017: Redox Biology
https://www.readbyqxmd.com/read/28815531/mitochondria-endoplasmic-reticulum-contact-sites-mediate-innate-immune-responses
#3
Takuma Misawa, Michihiro Takahama, Tatsuya Saitoh
Mitochondria and the endoplasmic reticulum (ER) are fundamental organelles that coordinate high-order cell functions. Mitochondria are centers of energy production, whereas the ER is responsible for folding, transport, and degradation of proteins. In addition to their specific functions, mitochondria and ER actively communicate with each other to promote a variety of cellular events, such as material transfer and signal transduction. Recent studies have shown the critical involvement of these organelles in regulation of the innate immune system, which functions in host defense...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28814662/irgm1-coordinately-regulates-autoimmunity-and-host-defense-at-select-mucosal-surfaces
#4
Kathleen M Azzam, Jennifer H Madenspacher, Derek W Cain, Lihua Lai, Kymberly M Gowdy, Prashant Rai, Kyathanahalli Janardhan, Natasha Clayton, Willie Cunningham, Heather Jensen, Preeyam S Patel, John F Kearney, Gregory A Taylor, Michael B Fessler
The pathogenesis of primary Sjogren's syndrome (SS), an autoimmune disease that targets the mucosa of exocrine tissues, is poorly understood. Although several mouse models have been developed that display features of SS, most of these are within the larger context of a lupus-like presentation. Immunity-related GTPase family M protein 1 (Irgm1) is an interferon-inducible cytoplasmic GTPase that is reported to regulate autophagy and mitochondrial homeostasis. Here, we report that naive Irgm1-/- mice display lymphocytic infiltration of multiple mucosal tissues including the lung in a manner reminiscent of SS, together with IgA class-predominant autoantibodies including anti-Ro and anti-La...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28811654/characterization-of-the-mollusc-rig-i-mavs-pathway-reveals-an-archaic-antiviral-signalling-framework-in-invertebrates
#5
Baoyu Huang, Linlin Zhang, Yishuai Du, Fei Xu, Li Li, Guofan Zhang
Despite the mitochondrial antiviral signalling protein (MAVS)-dependent RIG-I-like receptor (RLR) signalling pathway in the cytosol plays an indispensable role in the antiviral immunity of the host, surprising little is known in invertebrates. Here we characterized the major members of RLR pathway and investigated their signal transduction a Molluscs. We show that genes involved in RLR pathway were significantly induced during virus challenge, including CgRIG-I-1, CgMAVS, CgTRAF6 (TNF receptor-associated factor 6), and CgIRFs (interferon regulatory factors...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28810614/evolution-of-correlation-between-helicobacter-pylori-infection-and-autoimmune-liver-disease
#6
Xin-Guo Peng, Yu-Yuan Li, Hui-Ting Chen, Yan Zhou, Jian-Guo Ma, Hong-Min Yin
The present study was planned to evaluate correlation between Helicobacter pylori (HP) infection and autoimmune liver disease (AILD). A total of 60 patients diagnosed with AILD in Affiliated Hospital of Binzhou Medical College were continuously enrolled in the present study. HP infection was detected by 13C-urea breath test. The levels of anti-myeloperoxidase were tested by ELISA. The positive rate of anti-nuclear antibody (ANA), anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (SMA) and anti-neutrophil cytoplasm antibody (ANCA) were tested by indirect immunofluorescence...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808966/methods-to-visualize-mavs-subcellular-localization
#7
Christine Vazquez, Dia C Beachboard, Stacy M Horner
The mitochondrial antiviral signaling (MAVS) protein is a central adaptor protein required for antiviral innate immune signaling. To facilitate its roles in innate immunity, MAVS localizes to multiple intracellular membranous compartments, including the mitochondria, the mitochondrial-associated ER membrane (MAM), and peroxisomes. Studies of MAVS function therefore often require an analysis of MAVS localization. To detect MAVS protein on intracellular membranes, biochemical fractionation to isolate MAMs, mitochondria, or peroxisomes can be used...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28806642/circulating-follicular-helper-t-cells-presented-distinctively-different-responses-toward-bacterial-antigens-in-primary-biliary-cholangitis
#8
Zun-Qiang Zhou, Da-Nian Tong, Jiao Guan, Mei-Fang Li, Qi-Ming Feng, Min-Jie Zhou, Zheng-Yun Zhang
Primary biliary cholangitis (PBC) is a chronic and progressive cholestatic liver disease with unknown causes. The initiation of PBC is associated with bacterial infections and abnormal immune correlates, such as the presence of self-reactive anti-mitochondrial antibodies and shifted balance of T cell subsets. In particular, the CD4(+)CXCR5(+) follicular helper T (Tfh) cells are highly activated in PBC patients and are significantly associated with PBC severity, but the underlying reasons are unknown. In this study, we found that the circulating CD4(+)CXCR5(+) T cells were enriched with the interferon (IFN)-γ-secreting Th1-subtype and the interleukin (IL)-17-secreting Th17-subtype, but not the IL-4-secreting Th2 subtype...
August 11, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28806285/peritoneal-cavity-lavage-reduces-the-presence-of-mitochondrial-damage-associated-molecular-patterns-in-open-abdomen-patients
#9
Patricia Angellice Martinez-Quinones, Cameron Grant McCarthy, Caleb J Mentzer, Camilla Ferreira Wenceslau, Steven Barry Holsten, R Clinton Webb, Keith O'Malley
BACKGROUND: Mitochondrial damage-associated molecular patterns (mtDAMPs), such as mitochondrial DNA and N-formylated peptides, are endogenous molecules released from tissue after traumatic injury. mtDAMPs are potent activators of the innate immune system. They have similarities with bacteria, which allow mtDAMPs to interact with the same pattern recognition receptors and mediate the development of Systemic Inflammatory Response Syndrome (SIRS). Current recommendations for management of an open abdomen include returning to the operating room every 48 hours for peritoneal cavity lavage until definitive procedure...
August 12, 2017: Journal of Trauma and Acute Care Surgery
https://www.readbyqxmd.com/read/28801234/dendritic-cells-but-not-macrophages-sense-tumor-mitochondrial-dna-for-cross-priming-through-signal-regulatory-protein-%C3%AE-signaling
#10
Meng Michelle Xu, Yang Pu, Dali Han, Yaoyao Shi, Xuezhi Cao, Hua Liang, Xiang Chen, Xiao-Dong Li, Liufu Deng, Zhijian J Chen, Ralph R Weichselbaum, Yang-Xin Fu
Inhibition of cytosolic DNA sensing represents a strategy that tumor cells use for immune evasion, but the underlying mechanisms are unclear. Here we have shown that CD47-signal regulatory protein α (SIRPα) axis dictates the fate of ingested DNA in DCs for immune evasion. Although macrophages were more potent in uptaking tumor DNA, increase of DNA sensing by blocking the interaction of SIRPα with CD47 preferentially occurred in dendritic cells (DCs) but not in macrophages. Mechanistically, CD47 blockade enabled the activation of NADPH oxidase NOX2 in DCs, which in turn inhibited phagosomal acidification and reduced the degradation of tumor mitochondrial DNA (mtDNA) in DCs...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28798231/p2x7-receptor-antagonism-prevents-il-1%C3%AE-release-from-salivary-epithelial-cells-and-reduces-inflammation-in-a-mouse-model-of-autoimmune-exocrinopathy
#11
Mahmoud G Khalafalla, Lucas T Woods, Jean M Camden, Aslam A Khan, Kirsten H Limesand, Michael J Petris, Laurie Erb, Gary A Weisman
Salivary gland inflammation is a hallmark of Sjogrens syndrome (SS), a common autoimmune disease characterized by lymphocytic infiltration of the salivary gland and loss of saliva secretion, predominantly in women. The P2X7 receptor (P2X7R) is an ATP-gated non-selective cation channel that induces inflammatory responses in cells and tissues, including salivary gland epithelium. In immune cells, P2X7R activation induces the production of proinflammatory cytokines, including IL-1β and IL-18, by inducing the oligomerization of the multiprotein complex NLRP3-type inflammasome...
August 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28794148/tubulointerstitial-nephritis-with-igm-positive-plasma-cells
#12
Naoki Takahashi, Takako Saeki, Atsushi Komatsuda, Chishio Munemura, Takeaki Fukui, Naofumi Imai, Noriyuki Homma, Tsuguru Hatta, Ken-Ichi Samejima, Takashi Fujimoto, Hiroki Omori, Yumi Ito, Yudai Nishikawa, Mamiko Kobayashi, Yukie Morikawa, Sachiko Fukushima, Seiji Yokoi, Daisuke Mikami, Kenji Kasuno, Hideki Kimura, Tomoyuki Nemoto, Yasunari Nakamoto, Kiyonao Sada, Manabu Sugai, Hironobu Naiki, Haruyoshi Yoshida, Ichiei Narita, Yoshihiko Saito, Masayuki Iwano
Infiltration by IgG-positive plasma cells is a common finding in tubulointerstitial nephritis. Indeed, it has been thought that CD138-positive mature plasma cells secrete mainly IgG, and the occurrence of tubulointerstitial nephritis with CD138-positive plasma cells secreting IgM has rarely been reported. Routine immunofluorescence of fresh frozen sections is considered the gold standard for detection of immune deposits. However, the immunoenzyme method with formalin-fixed, paraffin-embedded sections is superior for detecting IgM- or IgG-positive cells within the renal interstitium, thus histologic variants may often go undetected...
August 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28791611/chronic-autoimmune-epithelitis-in-sj%C3%A3-gren-s-syndrome-and-primary-biliary-cholangitis-a-comprehensive-review
#13
REVIEW
Carlo Selmi, M Eric Gershwin
Within the spectrum of autoimmune diseases, Sjögren's syndrome and primary biliary cholangitis are exemplary and can be coined as chronic epithelitis based on their frequent coexistence in clinical practice and the highly specific immune-mediated injury of the small bile ducts and the exocrine glands. The pathogenic mechanisms underlying the diseases are similar, with apoptosis being the key element leading to organ-specific immune-mediated injury directed against the small bile ducts and salivary gland epithelia, respectively along with similar epidemiological features, such as female predominance and the age of onset in the fifth decade of life...
August 8, 2017: Rheumatology and Therapy
https://www.readbyqxmd.com/read/28783377/extracellular-mitochondrial-dna-is-generated-by-fibroblasts-and-predicts-death-in-idiopathic-pulmonary-fibrosis
#14
Changwan Ryu, Huanxing Sun, Mridu Gulati, Jose D Herazo-Maya, Yonglin Chen, Awo Osafo-Addo, Caitlin Brandsdorfer, Julia Winkler, Christina Blaul, Jaden Faunce, Hongyi Pan, Tony Woolard, Argyrios Tzouvelekis, Danielle E Antin-Ozerkis, Jonathan T Puchalski, Martin Slade, Anjelica L Gonzalez, Daniel F Bogenhagen, Varvara Kirillov, Carol Feghali-Bostwick, Kevin Gibson, Kathleen Lindell, Raimund I Herzog, Charles S Dela Cruz, Wajahat Mehal, Naftali Kaminski, Erica Herzog, Glenda Trujillo
RATIONALE: Idiopathic pulmonary fibrosis (IPF) involves the accumulation of alpha smooth muscle actin (αSMA) expressing myofibroblasts arising from interactions with soluble mediators such as transforming growth factor beta-1 (TGFβ1), and mechanical influences such as local tissue stiffness. While IPF fibroblasts are enriched for aerobic glycolysis and innate immune receptor activation, innate immune ligands related to mitochondrial injury, such as extracellular mitochondrial DNA (mtDNA) have not been identified in IPF...
August 7, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28780470/acrylamide-induces-immunotoxicity-through-reactive-oxygen-species-production-and-caspase-dependent-apoptosis-in-mice-splenocytes-via-the-mitochondria-dependent-signaling-pathways
#15
Ehsan Zamani, Fatemeh Shaki, Saeid AbedianKenari, Mohammad Shokrzadeh
INTRODUCTION: Acrylamide (AA), a well-known food neo-contamination, can be produced during food preparing at high temperature. The immunotoxicity of AA have been revealed in the experimental animals. In this study, we explored the molecular mechanism responsible for the immunotoxicity of AA. METHODS: The mice splenocytes exposed to AA concentrations (0,5,10 and 25 mM) and apoptosis cell death was measured through Annexin V/Propidium Iodide staining by flow cytometry method...
August 3, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28777108/genetics-in-inclusion-body-myositis
#16
Simon Rothwell, James B Lilleker, Janine A Lamb
PURPOSE OF REVIEW: To review the advances in our understanding of the genetics of inclusion body myositis (IBM) in the past year. RECENT FINDINGS: One large genetic association study focusing on immune-related genes in IBM has refined the association within the human leukocyte antigen (HLA) region to HLA-DRB1 alleles, and identified certain amino acid positions in HLA-DRB1 that may explain this risk. A suggestive association with CCR5 may indicate genetic overlap with other autoimmune diseases...
August 1, 2017: Current Opinion in Rheumatology
https://www.readbyqxmd.com/read/28774846/inhibited-fatty-acid-%C3%AE-oxidation-impairs-stress-resistance-ability-in-nile-tilapia-oreochromis-niloticus
#17
Han Pan, Ling-Yu Li, Jia-Min Li, Wei-Li Wang, Samwel Mchele Limbu, Pascal Degrace, Dong-Liang Li, Zhen-Yu Du
Energy metabolism plays important roles in stress resistance and immunity in mammals, however, such functions have not been established in fish. In the present study, Nile tilapia (Oreochromis niloticus) was fed with mildronate, an inhibitor of mitochondrial fatty acid (FA) β-oxidation, for six weeks subsequently challenged with Aeromonas hydrophila and ammonia nitrogen exposure. Mildronate treatment reduced significantly l-carnitine concentration and mitochondrial FA β-oxidation efficiency, while it increased lipid accumulation in liver...
July 31, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28771715/the-role-of-mitochondrial-ros-in-antibacterial-immunity
#18
REVIEW
Boris Pinegin, Nina Vorobjeva, Mikhail Pashenkov, Boris Chernyak
Reactive oxygen species (ROS) are essential participants of various innate immune cell responses against microorganisms and are also involved in many cellular regulatory pathways. It was believed that the main pool of ROS in the innate immune cells is generated by the NADPH oxidase enzymatic complex. However, it was discovered recently that mitochondrial ROS (mtROS) are equally important for the functioning of the immune system. mtROS play an important role in the development of the antimicrobial innate immune responses...
August 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28771279/superoxide-dismutase-2-is-dispensable-for-platelet-function
#19
Trevor P Fidler, Jesse W Rowley, Claudia Araujo, Luc H Boudreau, Alex Marti, Rhonda Souvenir, Kali Dale, Eric Boilard, Andrew S Weyrich, E Dale Abel
Increased intracellular reactive oxygen species (ROS) promote platelet activation. The sources of platelet-derived ROS are diverse and whether or not mitochondrial derived ROS, modulates platelet function is incompletely understood. Studies of platelets from patients with sickle cell disease, and diabetes suggest a correlation between mitochondrial ROS and platelet dysfunction. Therefore, we generated mice with a platelet specific knockout of superoxide dismutase 2 (SOD2-KO) to determine if increased mitochondrial ROS increases platelet activation...
August 3, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28768938/a-novel-molecular-model-of-plant-lectin-induced-programmed-cell-death-in-cancer
#20
Zheng Shi, Wen-Wen Li, Yong Tang, Li-Jia Cheng
Plant lectin, a class of highly diverse non-immune origin and carbohydrate-binding proteins, has been reported to specially induce cancer cell through programmed cell death (PCD) pathways (apoptosis and/or autophagy), shedding lights on screening promising anti-cancer candidate agent for further therapeutic trials. However, the complicated molecular mechanisms by which plant lectins induced the programmed death of tumor cells, have not yet been fully clarified. Here, we summarized a novel model, based on vast amount of research, by which plant lectins eliminate various types of cancer cells via three major pathways, including a) direct ribosome inactivating, b) endocytosis-dependent mitochondrial dysfunction and c) sugar-containing receptors binding...
August 1, 2017: Biological & Pharmaceutical Bulletin
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