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Immunopathology of viral

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https://www.readbyqxmd.com/read/28514692/interferon-%C3%AE-mediates-non-redundant-front-line-antiviral-protection-against-influenza-virus-infection-without-compromising-host-fitness
#1
Ioanna E Galani, Vasiliki Triantafyllia, Evridiki-Evangelia Eleminiadou, Ourania Koltsida, Athanasios Stavropoulos, Maria Manioudaki, Dimitris Thanos, Sean E Doyle, Sergei V Kotenko, Kalliopi Thanopoulou, Evangelos Andreakos
Lambda interferons (IFNλs) or type III IFNs share homology, expression patterns, signaling cascades, and antiviral functions with type I IFNs. This has complicated the unwinding of their unique non-redundant roles. Through the systematic study of influenza virus infection in mice, we herein show that IFNλs are the first IFNs produced that act at the epithelial barrier to suppress initial viral spread without activating inflammation. If infection progresses, type I IFNs come into play to enhance viral resistance and induce pro-inflammatory responses essential for confronting infection but causing immunopathology...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28487311/egr2-and-3-control-adaptive-immune-responses-by-temporally-uncoupling-expansion-from-t-cell-differentiation
#2
Tizong Miao, Alistair L J Symonds, Randeep Singh, Janine D Symonds, Ane Ogbe, Becky Omodho, Bo Zhu, Suling Li, Ping Wang
Egr2 and 3 are important for maintaining immune homeostasis. Here we define a fundamental function of Egr2 and 3 operating as a checkpoint that controls the transition between clonal expansion and differentiation of effector T cells. Egr2 and 3 deficiency resulted in defective clonal expansion but hyperactivation and excessive differentiation of T cells in response to viral infection. Conversely, sustained Egr2 expression enhanced expansion but severely impaired effector differentiation. Egr2 bound to and controlled the expression of genes regulating proliferation (Myc and Myb) and differentiation repressors (Bcl6, Id3), while repressing transcription factors required for effector function (Zeb2, RORa, RORc, and Bhlhe40)...
May 9, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28459437/host-dna-released-by-netosis-promotes-rhinovirus-induced-type-2-allergic-asthma-exacerbation
#3
Marie Toussaint, David J Jackson, Dawid Swieboda, Anabel Guedán, Theodora-Dorita Tsourouktsoglou, Yee Man Ching, Coraline Radermecker, Heidi Makrinioti, Julia Aniscenko, Michael R Edwards, Roberto Solari, Frédéric Farnir, Venizelos Papayannopoulos, Fabrice Bureau, Thomas Marichal, Sebastian L Johnston
Respiratory viral infections represent the most common cause of allergic asthma exacerbations. Amplification of the type-2 immune response is strongly implicated in asthma exacerbation, but how virus infection boosts type-2 responses is poorly understood. We report a significant correlation between the release of host double-stranded DNA (dsDNA) following rhinovirus infection and the exacerbation of type-2 allergic inflammation in humans. In a mouse model of allergic airway hypersensitivity, we show that rhinovirus infection triggers dsDNA release associated with the formation of neutrophil extracellular traps (NETs), known as NETosis...
May 1, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28448566/il-33-st2-pathway-drives-regulatory-t-cell-dependent-suppression-of-liver-damage-upon-cytomegalovirus-infection
#4
Branka Popovic, Mijo Golemac, Jürgen Podlech, Jelena Zeleznjak, Lidija Bilic-Zulle, Miodrag L Lukic, Luka Cicin-Sain, Matthias J Reddehase, Tim Sparwasser, Astrid Krmpotic, Stipan Jonjic
Regulatory T (Treg) cells dampen an exaggerated immune response to viral infections in order to avoid immunopathology. Cytomegaloviruses (CMVs) are herpesviruses usually causing asymptomatic infection in immunocompetent hosts and induce strong cellular immunity which provides protection against CMV disease. It remains unclear how these persistent viruses manage to avoid induction of immunopathology not only during the acute infection but also during life-long persistence and virus reactivation. This may be due to numerous viral immunoevasion strategies used to specifically modulate immune responses but also induction of Treg cells by CMV infection...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28406797/m1-like-monocytes-are-a-major-immunological-determinant-of-severity-in-previously-healthy-adults-with-life-threatening-influenza
#5
Suzanne L Cole, Jake Dunning, Wai Ling Kok, Kambez Hajipouran Benam, Adel Benlahrech, Emmanouela Repapi, Fernando O Martinez, Lydia Drumright, Timothy J Powell, Michael Bennett, Ruth Elderfield, Catherine Thomas, Tao Dong, John McCauley, Foo Y Liew, Stephen Taylor, Maria Zambon, Wendy Barclay, Vincenzo Cerundolo, Peter J Openshaw, Andrew J McMichael, Ling-Pei Ho
In each influenza season, a distinct group of young, otherwise healthy individuals with no risk factors succumbs to life-threatening infection. To better understand the cause for this, we analyzed a broad range of immune responses in blood from a unique cohort of patients, comprising previously healthy individuals hospitalized with and without respiratory failure during one influenza season, and infected with one specific influenza A strain. This analysis was compared with similarly hospitalized influenza patients with known risk factors (total of n = 60 patients recruited)...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28405622/m1-like-monocytes-are-a-major-immunological-determinant-of-severity-in-previously-healthy-adults-with-life-threatening-influenza
#6
Suzanne L Cole, Jake Dunning, Wai Ling Kok, Kambez Hajipouran Benam, Adel Benlahrech, Emmanouela Repapi, Fernando O Martinez, Lydia Drumright, Timothy J Powell, Michael Bennett, Ruth Elderfield, Catherine Thomas, Tao Dong, John McCauley, Foo Y Liew, Stephen Taylor, Maria Zambon, Wendy Barclay, Vincenzo Cerundolo, Peter J Openshaw, Andrew J McMichael, Ling-Pei Ho
In each influenza season, a distinct group of young, otherwise healthy individuals with no risk factors succumbs to life-threatening infection. To better understand the cause for this, we analyzed a broad range of immune responses in blood from a unique cohort of patients, comprising previously healthy individuals hospitalized with and without respiratory failure during one influenza season, and infected with one specific influenza A strain. This analysis was compared with similarly hospitalized influenza patients with known risk factors (total of n = 60 patients recruited)...
April 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28386004/reovirus-infection-triggers-inflammatory-responses-to-dietary-antigens-and-development-of-celiac-disease
#7
Romain Bouziat, Reinhard Hinterleitner, Judy J Brown, Jennifer E Stencel-Baerenwald, Mine Ikizler, Toufic Mayassi, Marlies Meisel, Sangman M Kim, Valentina Discepolo, Andrea J Pruijssers, Jordan D Ernest, Jason A Iskarpatyoti, Léa M M Costes, Ian Lawrence, Brad A Palanski, Mukund Varma, Matthew A Zurenski, Solomiia Khomandiak, Nicole McAllister, Pavithra Aravamudhan, Karl W Boehme, Fengling Hu, Janneke N Samsom, Hans-Christian Reinecker, Sonia S Kupfer, Stefano Guandalini, Carol E Semrad, Valérie Abadie, Chaitan Khosla, Luis B Barreiro, Ramnik J Xavier, Aylwin Ng, Terence S Dermody, Bana Jabri
Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (TH1) immunity against dietary gluten and celiac disease (CeD). To test this hypothesis and gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens, we developed a viral infection model that makes use of two reovirus strains that infect the intestine but differ in their immunopathological outcomes. Reovirus is an avirulent pathogen that elicits protective immunity, but we discovered that it can nonetheless disrupt intestinal immune homeostasis at inductive and effector sites of oral tolerance by suppressing peripheral regulatory T cell (pTreg) conversion and promoting TH1 immunity to dietary antigen...
April 7, 2017: Science
https://www.readbyqxmd.com/read/28384338/peripheral-and-central-immune-cell-reservoirs-in-tissues-from-asymptomatic-cats-chronically-infected-with-feline-immunodeficiency-virus
#8
C D Eckstrand, E E Sparger, K A Pitt, B G Murphy
Feline immunodeficiency virus (FIV) infection in cats results in life-long viral persistence and progressive immunopathology. We have previously described a cohort of experimentally infected cats demonstrating a progressive decline of peripheral blood CD4+ T-cell over six years in the face of apparent peripheral viral latency. More recently we reported findings from this same cohort that revealed popliteal lymph node tissue as sites for ongoing viral replication suggesting that tissue reservoirs are important in FIV immunopathogenesis during the late asymptomatic phase of infection...
2017: PloS One
https://www.readbyqxmd.com/read/28384263/universal-vaccine-against-respiratory-syncytial-virus-a-and-b-subtypes
#9
Jeong-Yoon Lee, Jun Chang
Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants, young children, and the elderly. Two subtypes of RSV, A and B, circulate alternately at 1-2-year intervals during epidemics. The attachment glycoprotein (G protein) of RSV is one of the major targets for immune responses. In this study, we generated a recombinant fusion protein, GcfAB, which consists of the central regions (a.a. residues 131-230) of the G proteins of both RSV A (A2 strain) and B (B1 strain) subtypes, and investigated immunogenicity, protective efficacy, and immunopathology...
2017: PloS One
https://www.readbyqxmd.com/read/28351919/contribution-of-the-purinergic-receptor-p2x7-to-development-of-lung-immunopathology-during-influenza-virus-infection
#10
Victor H Leyva-Grado, Megan E Ermler, Michael Schotsaert, Ma G Gonzalez, Virginia Gillespie, Jean K Lim, Adolfo García-Sastre
An exacerbated immune response is one of the main causes of influenza-induced lung damage during infection. The molecular mechanisms regulating the fate of the initial immune response to infection, either as a protective response or as detrimental immunopathology, are not well understood. The purinergic receptor P2X7 is an ionotropic nucleotide-gated ion channel receptor expressed on immune cells that has been implicated in induction and maintenance of excessive inflammation. Here, we analyze the role of this receptor in a mouse model of influenza virus infection using a receptor knockout (KO) mouse strain...
March 28, 2017: MBio
https://www.readbyqxmd.com/read/28344581/type-i-interferons-as-regulators-of-lung-inflammation
#11
REVIEW
Spyridon Makris, Michelle Paulsen, Cecilia Johansson
Immune responses to lung infections must be tightly regulated in order to permit pathogen eradication while maintaining organ function. Exuberant or dysregulated inflammation can impair gas exchange and underlies many instances of lung disease. An important driver of inflammation in the lung is the interferon (IFN) response. Type I IFNs are antiviral cytokines that induce a large range of proteins that impair viral replication in infected cells. This cell-intrinsic action plays a crucial role in protecting the lungs from spread of respiratory viruses...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28337195/nk-cells-uncertain-allies-against-malaria
#12
REVIEW
Asia-Sophia Wolf, Samuel Sherratt, Eleanor M Riley
Until recently, studies of natural killer (NK) cells in infection have focused almost entirely on their role in viral infections. However, there is an increasing awareness of the potential for NK cells to contribute to the control of a wider range of pathogens, including intracellular parasites such as Plasmodium spp. Given the high prevalence of parasitic diseases in the developing world and the devastating effects these pathogens have on large numbers of vulnerable people, investigating interactions between NK cells and parasitized host cells presents the opportunity to reveal novel immunological mechanisms with the potential to aid efforts to eradicate these diseases...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28322935/early-pathogenesis-during-infectious-bursal-disease-in-susceptible-chickens-is-associated-with-changes-in-b-cell-genomic-methylation-and-loss-of-genome-integrity
#13
Nick A Ciccone, Lorraine P Smith, William Mwangi, Amy Boyd, Andrew J Broadbent, Adrian L Smith, Venugopal Nair
We propose a model by which an increase in the genomic modification, 5-hydroxymethylcytosine (5hmC), contributes to B cell death within the chicken bursa of Fabricus (BF) infected with infectious bursal disease virus (IBDV). Our findings indicate that, following an IBDV infection, Rhode Island Red (RIR) chickens have fewer surviving B cells and higher levels of 5hmC in the BF than the more resistant 15l line of birds. Elevated genomic 5hmC levels within the RIR BF are associated with markers of immune responses: infiltrating T cells and increased expression of CD40L, FasL and iNOS...
August 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28283855/the-role-of-human-parainfluenza-virus-infections-in-the-immunopathology-of-the-respiratory-tract
#14
REVIEW
Malgorzata Pawełczyk, Marek Leszek Kowalski
Viral infections are leading causes of both upper and lower airway acute illness in all age groups of healthy persons, and have also been implicated in the acute exacerbations of chronic respiratory disorders like asthma and COPD. Human rhinovirus, respiratory syncytial virus, influenza virus and coronavirus have been considered as the most important respiratory pathogens and relatively little attention has been paid to the role of parainfluenza viruses (hPIVs). Human parainfluenza viruses are single-stranded RNA viruses belonging to the paramyxovirus family that may evoke lower respiratory infections in infants, children and immunocompromised individuals...
March 2017: Current Allergy and Asthma Reports
https://www.readbyqxmd.com/read/28273905/nkg2d-modulates-aggravation-of-liver-inflammation-by-activating-nk-cells-in-hbv-infection
#15
Yadong Wang, Wei Wang, Chuan Shen, Yong Wang, Mingjing Jiao, Weiyan Yu, Hongzhu Yin, Xiaobo Shang, Qianfei Liang, Caiyan Zhao
Hepatitis B virus (HBV) infection is thought to be an immune-mediated liver disease. The mechanisms underlying natural killer (NK) cell group 2D receptor (NKG2D) that activates NK cells and participates in anti-HBV immunity and immunopathology has not been thoroughly elucidated. Peripheral NKG2D(+) and IFN-γ(+) NK cells frequencies and intrahepatic NKG2D and IFN-γ mRNA and protein expressions were determined in HBV-infected patients. Levels of NKG2D and IFN-γ mRNA and protein in NK cells, co-cultured with HBV-replicating HepG2 cells with or without NKG2D blockade, were analyzed...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28261214/the-influence-of-the-microbiome-on-early-life-severe-viral-lower-respiratory-infections-and-asthma-food-for-thought
#16
REVIEW
Jason P Lynch, Md Al Amin Sikder, Bodie F Curren, Rhiannon B Werder, Jennifer Simpson, Páraic Ó Cuív, Paul G Dennis, Mark L Everard, Simon Phipps
Severe viral lower respiratory infections are a major cause of infant morbidity. In developing countries, respiratory syncytial virus (RSV)-bronchiolitis induces significant mortality, whereas in developed nations the disease represents a major risk factor for subsequent asthma. Susceptibility to severe RSV-bronchiolitis is governed by gene-environmental interactions that affect the host response to RSV infection. Emerging evidence suggests that the excessive inflammatory response and ensuing immunopathology, typically as a consequence of insufficient immunoregulation, leads to long-term changes in immune cells and structural cells that render the host susceptible to subsequent environmental incursions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28242695/genetic-variation-in-chromosome-y-regulates-susceptibility-to-influenza-a-virus-infection
#17
Dimitry N Krementsov, Laure K Case, Oliver Dienz, Abbas Raza, Qian Fang, Jennifer L Ather, Matthew E Poynter, Jonathan E Boyson, Janice Y Bunn, Cory Teuscher
Males of many species, ranging from humans to insects, are more susceptible than females to parasitic, fungal, bacterial, and viral infections. One mechanism that has been proposed to account for this difference is the immunocompetence handicap model, which posits that the greater infectious disease burden in males is due to testosterone, which drives the development of secondary male sex characteristics at the expense of suppressing immunity. However, emerging data suggest that cell-intrinsic (chromosome X and Y) sex-specific factors also may contribute to the sex differences in infectious disease burden...
March 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28214859/farnesoid-x-receptor-in-mice-prevents-severe-liver-immunopathology-during-lymphocytic-choriomeningitis-virus-infection
#18
Nadine Honke, Namir Shaabani, Cornelia Hardt, Caroline Krings, Dieter Häussinger, Philipp A Lang, Karl S Lang, Verena Keitel
BACKGROUND: Bile acids (BAs) are steroid molecules that are synthesized in the liver. In addition to their important role as a surfactant in solubilizing lipids and promoting the absorption of lipids in the gastrointestinal tract, they act as inflammagens. The role of BAs and their receptor farnesoid X receptor (FXR) during viral infection has not been studied in detail. METHODS: By using FXR-deficient mice, we investigated the role of bile acid receptor FXR during infection with lymphocytic choriomeningitis virus (LCMV)...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28207788/self-complementary-adeno-associated-virus-serotype-6-mediated-knockdown-of-adamts4-induces-long-term-and-effective-enhancement-of-aggrecan-in-degenerative-human-nucleus-pulposus-cells-a-new-therapeutic-approach-for-intervertebral-disc-disorders
#19
Demissew Shenegelegn Mern, Anja Tschugg, Sebastian Hartmann, Claudius Thomé
Inhibition of intervertebral disc (IVD) degeneration, which is often accompanied by painful inflammatory and immunopathological processes, is challenging. Current IVD gene therapeutic approaches are based on adenoviral gene delivery systems, which are limited by immune reactions to their viral proteins. Their applications in IVDs near to sensitive neural structure could provoke toxicity and immunological side-effects with neurological deficits. Self-complementary adeno-associated virus (scAAV) vectors, which do not express any viral gene and are not linked with any known disease in humans, are attractive therapeutic gene delivery vectors in degenerative IVDs...
2017: PloS One
https://www.readbyqxmd.com/read/28169000/regulation-and-functions-of-nlrp3-inflammasome-during-influenza-virus-infection
#20
Teneema Kuriakose, Thirumala-Devi Kanneganti
The NLRP3 inflammasome constitutes a major antiviral host defense mechanism during influenza virus infection. Inflammasome assembly in virus-infected cells facilitates autocatalytic processing of pro-caspase-1 and subsequent cleavage and secretion of proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is critical for induction of both innate and adaptive immune responses during influenza virus infection. Inflammasome-dependent antiviral responses also regulate immunopathology and tissue repair in the infected lungs...
February 3, 2017: Molecular Immunology
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