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Innate immunity

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https://www.readbyqxmd.com/read/27933565/kshv-strategies-for-host-dsdna-sensing-machinery
#1
REVIEW
Hang Gao, Yanyan Song, Chengrong Liu, Qiming Liang
The innate immune system utilizes pattern recognition receptors cyclic GMP-AMP synthase (cGAS) to sense cytosolic double-stranded (ds) DNA and initiate type 1 interferon signaling and autophagy pathway, which collaborate to limit pathogen infections as well as alarm the adaptive immune response. The genomes of herpesviruses are large dsDNA, which represent a major class of pathogen signatures recognized by cellular DNA sensor cGAS. However, to successfully establish the persistent infection, herpesviruses have evolved their viral genes to modulate different aspects of host immune signaling...
December 5, 2016: Virologica Sinica
https://www.readbyqxmd.com/read/27933307/impact-of-intravenous-infusion-time-on-aav8-vector-pharmacokinetics-safety-and-liver-transduction-in-cynomolgus-macaques
#2
Jenny A Greig, Jayme Ml Nordin, Erin Bote, Leah Makaron, Mason E Garnett, Lisa M Kattenhorn, Peter Bell, Tamara Goode, James M Wilson
Systemically delivered adeno-associated viral (AAV) vectors are now in early-phase clinical trials for a variety of diseases. While there is a general consensus on inclusion and exclusion criteria for each of these trials, the conditions under which vectors are infused vary significantly. In this study, we evaluated the impact of intravenous infusion rate of AAV8 vector in cynomolgus macaques on transgene expression, vector clearance from the circulation, and potential activation of the innate immune system...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27933067/peptide-idr-1002-inhibits-nf-%C3%AE%C2%BAb-nuclear-translocation-by-inhibition-of-i%C3%AE%C2%BAb%C3%AE-degradation-and-activates-p38-erk1-2-msk1-dependent-creb-phosphorylation-in-macrophages-stimulated-with-lipopolysaccharide
#3
Alejandro Huante-Mendoza, Octavio Silva-García, Javier Oviedo-Boyso, Robert E W Hancock, Víctor M Baizabal-Aguirre
The inflammatory response is a critical molecular defense mechanism of the innate immune system that mediates the elimination of disease-causing bacteria. Repair of the damaged tissue, and the reestablishment of homeostasis, must be accomplished after elimination of the pathogen. The innate defense regulators (IDRs) are short cationic peptides that mimic natural host defense peptides and are effective in eliminating pathogens by enhancing the activity of the immune system while controlling the inflammatory response...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27933059/formation-of-neutrophil-extracellular-traps-under-low-oxygen-level
#4
Katja Branitzki-Heinemann, Helene Möllerherm, Lena Völlger, Diab M Husein, Nicole de Buhr, Stefanie Blodkamp, Friederike Reuner, Graham Brogden, Hassan Y Naim, Maren von Köckritz-Blickwede
Since their discovery, neutrophil extracellular traps (NETs) have been characterized as a fundamental host innate immune defense mechanism. Conversely, excessive NET-release may have a variety of detrimental consequences for the host. A fine balance between NET formation and elimination is necessary to sustain a protective effect during an infectious challenge. Our own recently published data revealed that stabilization of hypoxia-inducible factor 1α (HIF-1α) by the iron chelating HIF-1α-agonist desferoxamine or AKB-4924 enhanced the release of phagocyte extracellular traps...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27932997/characterization-of-reproductive-dormancy-in-male-drosophila-melanogaster
#5
Olga I Kubrak, Lucie Kučerová, Ulrich Theopold, Sören Nylin, Dick R Nässel
Insects are known to respond to seasonal and adverse environmental changes by entering dormancy, also known as diapause. In some insect species, including Drosophila melanogaster, dormancy occurs in the adult organism and postpones reproduction. This adult dormancy has been studied in female flies where it is characterized by arrested development of ovaries, altered nutrient stores, lowered metabolism, increased stress and immune resistance and drastically extended lifespan. Male dormancy, however, has not been investigated in D...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27932942/loss-of-fractalkine-signaling-exacerbates-axon-transport-dysfunction-in-a-chronic-model-of-glaucoma
#6
Kevin T Breen, Sarah R Anderson, Michael R Steele, David J Calkins, Alejandra Bosco, Monica L Vetter
Neurodegeneration in glaucoma results in decline and loss of retinal ganglion cells (RGCs), and is associated with activation of myeloid cells such as microglia and macrophages. The chemokine fractalkine (FKN or Cx3cl1) mediates communication from neurons to myeloid cells. Signaling through its receptor Cx3cr1 has been implicated in multiple neurodegenerative diseases, but the effects on neuronal pathology are variable. Since it is unknown how FKN-mediated crosstalk influences RGC degeneration in glaucoma, we assessed this in a chronic mouse model, DBA/2J...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27932773/-effect-of-nlrp3-inflammasome-on-vascular-diseases
#7
Zeng Cao, Yapei Li, Ruifang Chen, Pingyu Zeng
The NLRP3 inflammasome, a protein complex belonging to the family of nucleotide-binding and oligomerization domain like receptors (NLRs), plays a vital role in the innate immune system. It promotes pro-caspase 1 cleavage into active caspase-1, which contributes to maturation and releases of IL-1β and IL-18 in response to the harmful signals and participates in the host immune response and sterile inflammation. Recently a large number of studies have shown that NLRP3 inflammasome closely relates to the pathogenesis of the vascular diseases...
November 28, 2016: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/27932622/inflammasome-activation-underlies-central-nervous-system-deterioration-in-hiv-associated-tuberculosis
#8
Suzaan Marais, Rachel P J Lai, Katalin A Wilkinson, Graeme Meintjes, Anne O'Garra, Robert J Wilkinson
Tuberculosis meningitis (TBM) is a frequent cause of meningitis in HIV-infected individuals, resulting in death in ~ 40% of affected patients. A severe complication of antiretroviral therapy (ART) in these patients is neurological TB-immune reconstitution inflammatory syndrome (IRIS), but its underlying cause remains poorly understood. To investigate the pathogenesis of TBM-IRIS, we performed longitudinal whole blood microarray analysis of HIV-infected TBM patients and reflected the findings at the protein level...
December 8, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27932462/salmonella-co-opts-host-cell-chaperone-mediated-autophagy-for-intracellular-growth
#9
Vikash Singh, Johannes Finke-Isami, Amanda C Hopper-Chidlaw, Peter Schwerk, Arthur Thompson, Karsten Tedin
Salmonella enterica are invasive, intracellular pathogens which replicate within a membrane-bound compartment inside infected host cells known as the Salmonella-containing vacuole (SCV). How Salmonella obtains nutrients for growth within this intracellular niche despite the apparent isolation is currently not known. Recent studies have indicated the importance of glucose and related carbon sources for tissue colonisation and intracellular proliferation within host cells during Salmonella infections, although none have been found to be essential...
December 8, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27932349/nadph-oxidase-2-and-atherothrombosis-insight-from-chronic-granulomatous-disease
#10
REVIEW
Francesco Violi, Roberto Carnevale, Lorenzo Loffredo, Pasquale Pignatelli, John I Gallin
The phagocytic cell enzyme NADPH oxidase-2 (Nox2) is critical for killing micro-organisms via production of reactive oxygen species and thus is a key element of the innate immune system. Nox2 is also detectable in endothelial cells and platelets where it has vasoconstrictive and aggregating properties, respectively. Patients with X-linked chronic granulomatous disease with hereditary Nox2 deficiency not only have impaired bacterial killing but, in association with loss of Nox2 function, also have enhanced carotid artery dilation, impaired platelet-related thrombosis, and reduced carotid atherosclerotic burden...
December 8, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27931844/dendritic-cells-in-hematological-malignancies
#11
REVIEW
Domenico Galati, Gaetano Corazzelli, Rosaria De Filippi, Antonio Pinto
Dendritic cells (DCs) are bone-marrow-derived immune cells accounted for a crucial role in initiating and modulating the adaptive immune response and supporting the innate immune response independently from T cells. While functioning as the most effective antigen-presenting cells within the immune system, DCs can otherwise induce tolerance in central and peripheral lymphoid organs acting therefore as suppressors rather than stimulators of the immune response. Within mechanisms regulating antitumor immunity, DCs can capture antigens from viable or damaged tumor cells and present the processed peptides to T-cells to prompt the generation and maintenance of an effective tumor-specific T-cell response...
December 2016: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/27931776/cd47-deficiency-improves-neurological-outcomes-of-traumatic-brain-injury-in-mice
#12
Song Zhao, Zhanyang Yu, Yu Liu, Yang Bai, Yinghua Jiang, Klaus van Leyen, Yong-Guang Yang, Josephine M Lok, Michael J Whalen, Eng H Lo, Xiaoying Wang
CD47 is a receptor for signal-regulatory protein alpha (SIRPα) in self-recognition by the innate immune system, and a receptor of thrombospondin-1 (TSP-1) contributing to vascular impairment in response to stress. However, the roles of CD47 in traumatic brain injury (TBI) have not been investigated. In this study we aimed to test our hypothesis that CD47 mediates early neutrophil brain infiltration and late brain vascular remodeling after TBI. Mice were subjected to TBI using a controlled cortical impact (CCI) device...
December 5, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27931684/inhibition-of-apoptosis-by-rv2456c-through-nuclear-factor-%C3%AE%C2%BAb-extends-the-survival-of-mycobacterium-tuberculosis
#13
Kristen L Jurcic Smith, Sunhee Lee
Mycobacterium tuberculosis, the causative agent of tuberculosis, is an intracellular pathogen with several survival mechanisms aimed at subverting the host immune system. Apoptosis has been shown to be mycobactericidal, to activate CD8(+) T cells, and to be modulated by mycobacterial proteins. Since few mycobacterial proteins have so far been directly implicated in the interactions between M. tuberculosis and host cell apoptosis, we screened M. tuberculosis H37Rv transposon mutants to identify mutants that fail to inhibit cell death (FID)...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27931588/evaluation-of-mannose-binding-lectin-is-a-useful-approach-to-predict-the-risk-of-infectious-complications-following-autologous-hematopoietic-stem-cell-transplantation
#14
Z B Radnay, M Udvardy, M Papp, J Hársfalvi, L Rejto, I Pál, Á Illés, A Kiss
Hematopoietic stem cell transplantation (HSCT) associated immunocompromised state carries high risk of infectious complications. Mannose-binding lectin (MBL) is an acute phase protein involved in innate immune response. Serum MBL level is genetically determined and quite stable. According to literature, significant association was shown between low MBL concentrations and serious infections. The association between serum MBL level and frequency and severity of infections was studied in 186 patients following autologous HSCT...
December 2016: Transplantation Proceedings
https://www.readbyqxmd.com/read/27931536/advances-in-atopic-dermatitis-in-2015
#15
REVIEW
Takashi Nomura, Kenji Kabashima
This review aims to highlight recently published articles on atopic dermatitis (AD). Updated are the insights into epidemiology, pathology, diagnostics, and therapy. Epidemiologic studies have revealed a positive correlation between AD and systemic conditions, such as rheumatoid arthritis, inflammatory bowel disease, and neonatal adiposity. Pathologic findings highlight the involvement of novel barrier factors (desmoplakin and claudin), novel immune cell subsets (pathogenic effector TH2 cells and group 2 innate lymphoid cells), and differential skewing of helper T cells (eg, TH17 dominance in Asians with AD)...
December 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27931217/lrp1-modulates-the-microglial-immune-response-via-regulation-of-jnk-and-nf-%C3%AE%C2%BAb-signaling-pathways
#16
Longyu Yang, Chia-Chen Liu, Honghua Zheng, Takahisa Kanekiyo, Yuka Atagi, Lin Jia, Daxin Wang, Aurelie N'songo, Dan Can, Huaxi Xu, Xiao-Fen Chen, Guojun Bu
BACKGROUND: Neuroinflammation is characterized by microglial activation and the increased levels of cytokines and chemokines in the central nervous system (CNS). Recent evidence has implicated both beneficial and toxic roles of microglia when over-activated upon nerve injury or in neurodegenerative diseases, including Alzheimer's disease (AD). The low-density lipoprotein receptor-related protein 1 (LRP1) is a major receptor for apolipoprotein E (apoE) and amyloid-β (Aβ), which play critical roles in AD pathogenesis...
December 8, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27930745/the-ebola-interferon-inhibiting-domains-attenuate-and-dysregulate-cell-mediated-immune-responses
#17
Ndongala Michel Lubaki, Patrick Younan, Rodrigo I Santos, Michelle Meyer, Mathieu Iampietro, Richard A Koup, Alexander Bukreyev
Ebola virus (EBOV) infections are characterized by deficient T-lymphocyte responses, T-lymphocyte apoptosis and lymphopenia. We previously showed that disabling of interferon-inhibiting domains (IIDs) in the VP24 and VP35 proteins effectively unblocks maturation of dendritic cells (DCs) and increases the secretion of cytokines and chemokines. Here, we investigated the role of IIDs in adaptive and innate cell-mediated responses using recombinant viruses carrying point mutations, which disabled IIDs in VP24 (EBOV/VP24m), VP35 (EBOV/VP35m) or both (EBOV/VP35m/VP24m)...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27929668/cd40-signaling-in-graves-disease-is-mediated-through-canonical-and-non-canonical-thyroidal-nf-%C3%AE%C2%BAb-activation
#18
Hanna J Lee, Angela Lombardi, Mihaela Stefan, Cheuk Wun Li, William B Inabnet, Randall P Owen, Erlinda Concepcion, Yaron Tomer
CD40, a tumor necrosis factor receptor, is a major immune-modulating susceptibility gene for Graves' disease (GD) as well as for a variety of other autoimmune diseases. Its broad association with autoimmunity underscores its paramount role in the development of a normal adaptive immune response, primarily in coordinating effective antigen presentation. The molecular pathways by which CD40 activation in the thyroid induces GD are unknown. In this study, we investigated whether NF-κB, a ubiquitious family of transcription factors, mediates the downstream effects of thyroid-specific CD40 activation...
December 8, 2016: Endocrinology
https://www.readbyqxmd.com/read/27929078/gut-microbiota-from-metabolic-disease-resistant-macrophage-specific-rip140-knockdown-mice-improves-metabolic-phenotype-and-gastrointestinal-integrity
#19
Yi-Wei Lin, Emmanuel Montassier, Dan Knights, Li-Na Wei
While fecal microbiota transplantation (FMT) presents an attractive therapeutic strategy, it remains unclear how to choose the microbiota repertoire that most effectively transfers benefit to recipients. We identified a beneficial taxonomic repertoire in a transgenic mouse model (RIP140mϕKD) which resists the development of high fat diet (HFD)-induced metabolic diseases due to enhanced anti-inflammation engineered by lowering receptor interacting protein (RIP140) expression in macrophage. We confirmed using FMT from HFD-fed RIP140mϕKD to wild type (WT) mice that recipient mice acquired the microbiota repertoire of donor mice...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27929056/gsk-3%C3%AE-controls-nf-kappab-activity-via-ikk%C3%AE-nemo
#20
Senad Medunjanin, Lisa Schleithoff, Christian Fiegehenn, Soenke Weinert, Werner Zuschratter, Ruediger C Braun-Dullaeus
The NF-κB signaling pathway is central for the innate immune response and its deregulation is found in multiple disorders such as autoimmune, chronic inflammatory and metabolic diseases. IKKγ/NEMO is essential for NF-κB activation and NEMO dysfunction in humans has been linked to so-called progeria syndromes, which are characterized by advanced ageing due to age-dependent inflammatory diseases. It has been suggested that glycogen synthase kinase-3β (GSK-3β) participates in NF-κB regulation but the exact mechanism remained incompletely understood...
December 8, 2016: Scientific Reports
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