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Immunopathology of viral

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https://www.readbyqxmd.com/read/28214859/farnesoid-x-receptor-in-mice-prevents-severe-liver-immunopathology-during-lymphocytic-choriomeningitis-virus-infection
#1
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)...
January 25, 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
#2
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
#3
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
https://www.readbyqxmd.com/read/28157451/the-role-of-nod-like-receptors-in-pulmonary-infection
#4
Kristin M Wiese, Bria M Coates, Karen M Ridge
Pneumonia is caused by both viral and bacterial pathogens and is responsible for a significant health burden in the Unites States. The innate immune system is the human body's first line of defense against these pathogens. The recognition of invading pathogens via pattern recognition receptors (PRRs) leads to proinflammatory cytokine and chemokine production followed by recruitment and activation of effector immune cells. The nonspecific inflammatory nature of the innate immune response can result in immunopathology that is detrimental to the host...
February 3, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28138136/t-cell-responses-in-the-central-nervous-system
#5
REVIEW
Thomas Korn, Axel Kallies
T cells are required for immune surveillance of the central nervous system (CNS); however, they can also induce severe immunopathology in the context of both viral infections and autoimmunity. The mechanisms that are involved in the priming and recruitment of T cells to the CNS are only partially understood, but there has been renewed interest in this topic since the 'rediscovery' of lymphatic drainage from the CNS. Moreover, tissue-resident memory T cells have been detected in the CNS and are increasingly recognized as an autonomous line of host defence...
January 31, 2017: Nature Reviews. Immunology
https://www.readbyqxmd.com/read/28134626/regional-astrocyte-ifn-signaling-restricts-pathogenesis-during-neurotropic-viral-infection
#6
Brian P Daniels, Harsha Jujjavarapu, Douglas M Durrant, Jessica L Williams, Richard R Green, James P White, Helen M Lazear, Michael Gale, Michael S Diamond, Robyn S Klein
Type I IFNs promote cellular responses to viruses, and IFN receptor (IFNAR) signaling regulates the responses of endothelial cells of the blood-brain barrier (BBB) during neurotropic viral infection. However, the role of astrocytes in innate immune responses of the BBB during viral infection of the CNS remains to be fully elucidated. Here, we have demonstrated that type I IFNAR signaling in astrocytes regulates BBB permeability and protects the cerebellum from infection and immunopathology. Mice with astrocyte-specific loss of IFNAR signaling showed decreased survival after West Nile virus infection...
January 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28129034/alkyl-polyglycoside-a-highly-promising-adjuvant-in-intranasal-split-influenza-vaccines
#7
Hui Wu, Yuanyuan Bao, Xiang Wang, Dongming Zhou, Wenzhe Wu
Influenza viral infections are significant global public health concerns due to the morbidity and mortality associated with acute respiratory disease, secondary complications, and pandemic threats; thus, continuous efforts have been made to develop potent influenza vaccines. In this study, three different mucosal adjuvants-alkyl polyglycoside (APG), gellan gum, and chitosan (CS)-were evaluated for their efficacy in intranasal A/H1N1 or B split influenza vaccines administered to BALB/c mice. Protective immunity was monitored by serum analysis for IgG, hemagglutination inhibition (HI), and neutralizing antibody levels, as well as mucosal IgA levels in nasal and pulmonary lavage fluids...
January 27, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28116826/mechanistic-perspective-of-the-oxido-immunopathologic-resolution-property-of-kolaviron-in-mice-influenza-pneumonitis
#8
Ifeoluwa O Awogbindin, David O Olaleye, Ebenezer O Farombi
Implicated in influenza-associated pathology are innate defence overzealousness and unabated secretion of oxidative tissue-sensitive antimicrobial agents. At different time points, mice were pre-treated with kolaviron (400 mg/kg), a natural antioxidant and anti-inflammatory agent, and subsequently challenged with 2 LD50 influenza A/H3N2/Perth/16/09 virus. After euthanasia at day 6, blood, lungs, liver and spleen were collected and processed for biochemical, immunohistochemical and flow cytometric assessment of redo-inflammatory imbalance, cytokine storm indices and T helper 1 host response...
January 23, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28077598/notch-ligand-delta-like-4-promotes-regulatory-t-cell-identity-in-pulmonary-viral-infection
#9
Hung-An Ting, Matthew A Schaller, Denise E de Almeida Nagata, Andrew J Rasky, Ivan P Maillard, Nicholas W Lukacs
Regulatory T (Treg) cells establish tolerance, prevent inflammation at mucosal surfaces, and regulate immunopathology during infectious responses. Recent studies have shown that Delta-like ligand 4 (Dll4) was upregulated on APC after respiratory syncytial virus (RSV) infection, and its inhibition leads to exaggerated immunopathology. In the present study, we outline the role of Dll4 in Treg cell differentiation, stability, and function in RSV infection. We found that Dll4 was expressed on CD11b(+) pulmonary dendritic cells in the lung and draining lymph nodes in wild-type BALB/c mice after RSV infection...
February 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28031333/t-cells-infiltrating-diseased-liver-express-ligands-for-the-nkg2d-stress-surveillance-system
#10
Wei-Chen Huang, Nicholas J Easom, Xin-Zi Tang, Upkar S Gill, Harsimran Singh, Francis Robertson, Chiwen Chang, John Trowsdale, Brian R Davidson, William M Rosenberg, Giuseppe Fusai, Antoine Toubert, Patrick T Kennedy, Dimitra Peppa, Mala K Maini
NK cells, which are highly enriched in the liver, are potent regulators of antiviral T cells and immunopathology in persistent viral infection. We investigated the role of the NKG2D axis in T cell/NK cell interactions in hepatitis B. Activated and hepatitis B virus (HBV)-specific T cells, particularly the CD4 fraction, expressed NKG2D ligands (NKG2DL), which were not found on T cells from healthy controls (p < 0.001). NKG2DL-expressing T cells were strikingly enriched within HBV-infected livers compared with the periphery or to healthy livers (p < 0...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28017800/viral-mouse-models-of-multiple-sclerosis-and-epilepsy-marked-differences-in-neuropathogenesis-following-infection-with-two-naturally-occurring-variants-of-theiler-s-virus-bean-strain
#11
Sonja Bröer, Elias Hage, Christopher Käufer, Ingo Gerhauser, Muneeb Anjum, Lin Li, Wolfgang Baumgärtner, Thomas F Schulz, Wolfgang Löscher
Following intracerebral inoculation, the BeAn 8386 strain of Theiler's virus causes persistent infection and inflammatory demyelinating encephalomyelitis in the spinal cord of T-cell defective SJL/J mice, which is widely used as a model of multiple sclerosis. In contrast, C57BL/6 (B6) mice clear the virus and develop inflammation and lesions in the hippocampus, associated with acute and chronic seizures, representing a novel model of viral encephalitis-induced epilepsy. Here we characterize the geno- and phenotype of two naturally occurring variants of BeAn (BeAn-1 and BeAn-2) that can be used to further understand the viral and host factors involved in the neuropathogenesis in B6 and SJL/J mice...
December 22, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/28003150/concomitant-helminth-infection-downmodulates-the-vaccinia-virus-specific-immune-response-and-potentiates-virus-associated-pathology
#12
Pedro Henrique Gazzinelli-Guimarães, Lorena Falabella Daher de Freitas, Ana Clara Gazzinelli-Guimarães, Fabiana Coelho, Fernando Sérgio Barbosa, Denise Nogueira, Chiara Amorim, Lucas de Carvalho Dhom-Lemos, Luciana Maria Oliveira, Alexandre Barcelos da Silveira, Flávio Guimarães da Fonseca, Lilian Lacerda Bueno, Ricardo Toshio Fujiwara
The aim of this work was to elucidate the immunopathological mechanisms of how helminths may influence the course of a viral infection, using a murine model. Severe virulence, a relevant increase in the virus titres in the lung and a higher mortality rate were observed in Ascaris and Vaccinia virus (VACV) co-infected mice, compared with VACV mono-infected mice. Immunopathological analysis suggested that the ablation of CD8(+) T cells, the marked reduction of circulating CD4(+) T cells producing IFN-γ, and the robust pulmonary inflammation were associated with the increase of morbidity/mortality in co-infection and subsequently with the negative impact of concomitant pulmonary ascariasis and respiratory VACV infection for the host...
December 18, 2016: International Journal for Parasitology
https://www.readbyqxmd.com/read/27994594/type-i-interferon-impairs-specific-antibody-responses-early-during-establishment-of-lcmv-infection
#13
Matthieu Daugan, Armstrong Murira, Barbara C Mindt, Amélie Germain, Esther Tarrab, Pascal Lapierre, Jörg H Fritz, Alain Lamarre
Elicitation of type I interferon (IFN-I) has been shown to both enhance and impair cell-mediated immune responses in acute and persistent viral infections, respectively. Here, we show that, in addition to its effect on T cells, IFN-I drives impairment of specific antibody responses through interaction with B cells in the acute phase of lymphocytic choriomeningitis virus (LCMV) infection. This impairment was limited to the T cell-dependent B cell response and was associated with disruption of B cell follicles, development of hypergammaglobulinemia (HGG), and expansion of the T follicular helper cell population...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27993116/molecular-approaches-target-to-immunotherapy-for-hpv-associated-cancers
#14
Fang Zhou, Lifang Zhang, Kong-Nan Zhao
Infection with human papillomavirus (HPVs) causes many cancers, which account for about 10-20% of total human cancers. Two recently developed prophylactic vaccines against virus infection confer strong immunogenicity to provide long-term protection. The use of these vaccines has contributed to a substantial decrease in the rates of cervical cancer the second most common cancer of women worldwide. However, therapeutic vaccines that can eliminate pre-existing HPV infections and treat an existing HPV- caused cancer have not been developed...
December 15, 2016: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/27966555/reversal-of-trem-1-ectodomain-shedding-and-improved-bacterial-clearance-by-intranasal-metalloproteinase-inhibitors
#15
G Weiss, C Lai, M E Fife, A M Grabiec, B Tildy, R J Snelgrove, G Xin, C M Lloyd, T Hussell
Triggering receptor expressed on myeloid cells-1 (TREM-1) is expressed on neutrophils and monocyte/macrophages and amplifies Toll-like receptor-mediated inflammation during infection. TREM-1 also exists in an antagonistic soluble form (sTREM-1) that has been used as a peripheral biomarker in sepsis, though the mechanisms of its release are not entirely clear. The requirement of TREM-1 in single microbial infections is controversial, with some studies showing a protective role and others a contribution to immunopathology...
December 14, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27922126/viral-and-bacterial-co-infection-in-severe-pneumonia-triggers-innate-immune-responses-and-specifically-enhances-ip-10-a-translational-study
#16
Jonathan Hoffmann, Daniela Machado, Olivier Terrier, Stephane Pouzol, Mélina Messaoudi, Wilma Basualdo, Emilio E Espínola, Rosa M Guillen, Manuel Rosa-Calatrava, Valentina Picot, Thomas Bénet, Hubert Endtz, Graciela Russomando, Gláucia Paranhos-Baccalà
Mixed viral and bacterial infections are widely described in community-acquired pneumonia; however, the clinical implications of co-infection on the associated immunopathology remain poorly studied. In this study, microRNA, mRNA and cytokine/chemokine secretion profiling were investigated for human monocyte-derived macrophages infected in-vitro with Influenza virus A/H1N1 and/or Streptococcus pneumoniae. We observed that the in-vitro co-infection synergistically increased interferon-γ-induced protein-10 (CXCL10, IP-10) expression compared to the singly-infected cells conditions...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27920778/the-dynamics-of-t-and-b-cells-in-lymph-node-during-chronic-hiv-infection-tfh-and-hiv-unhappy-dance-partners
#17
REVIEW
Jung Joo Hong, Kyu-Tae Chang, Francois Villinger
Although the dynamics of germinal center (GC) formation, follicular helper T (TFH) cell recruitment to B cell follicles within lymphoid organs, and changes of lymphoid tissue architecture in HIV/SIV infection have been documented, the underlying immunopathology remains unclear. Here, we summarize what is known regarding the kinetics of TFH cells and GC B cells during the course of infection as well as the potential immunopathological features associated with structural changes in the lymphoid compartment. This review also explores the implications of cell dynamics in the formation and maintenance of viral reservoirs in hyperplastic follicles of secondary lymphoid organs before and after viral suppressive antiretroviral therapy...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27903736/t-and-b-cell-markers-in-dried-blood-spots-of-neonates-with-congenital-cytomegalovirus-infection-b-cell-numbers-at-birth-are-associated-with-long-term-outcomes
#18
Roberta Rovito, Marjolein J Korndewal, Menno C van Zelm, Dimitrios Ziagkos, Els Wessels, Mirjam van der Burg, Aloys C M Kroes, Anton W Langerak, Ann C T M Vossen
Congenital CMV infection (cCMV) is the most common congenital infection that can cause long-term impairment (LTI). The pathogenesis of LTI is not completely understood. Fetal immunity may play a role in controlling the infection and preventing LTI, although immune activation may also contribute to fetal immunopathology. In this study, we analyzed various molecular markers of T and B cell numbers in neonatal dried blood spots of 99 children with cCMV and 54 children without cCMV: δRec-ψJα signal joints on TCR excision circles, intron recombination signal sequence k-deleting element signal joints on Igκ-deleting recombination excision circles, genomic intron recombination signal sequence k-deleting element coding joint, genomic Vδ1-Jδ1, and Vδ2-Jδ1 rearrangements...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27855206/zika-prvabc59-infection-is-associated-with-t-cell-infiltration-and-neurodegeneration-in-cns-of-immunocompetent-neonatal-c57bl-6-mice
#19
Mohanraj Manangeeswaran, Derek D C Ireland, Daniela Verthelyi
The recent spread of Zika virus (ZIKV) and its association with increased rates of Guillain Barre and other neurological disorders as well as congenital defects that include microcephaly has created an urgent need to develop animal models to examine the pathogenesis of the disease and explore the efficacy of potential therapeutics and vaccines. Recently developed infection models for ZIKV utilize mice defective in interferon responses. In this study we establish and characterize a new model of peripheral ZIKV infection using immunocompetent neonatal C57BL/6 mice and compare its clinical progression, virus distribution, immune response, and neuropathology with that of C57BL/6-IFNAR KO mice...
November 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27852848/age-dependent-differences-in-pseudorabies-virus-neuropathogenesis-and-associated-cytokine-expression
#20
Sara Verpoest, Brigitte Cay, Herman Favoreel, Nick De Regge
: The severity of clinical symptoms induced by pseudorabies virus (PRV) infection of its natural host is inversely related to the age of the pig. During this study, 2- and 15-week-old pigs were inoculated with PRV strain NIA3. This resulted in important clinical disease, although the associated morbidity and mortality were lower in older pigs. Quantitative PCR analysis of viral DNA in different organs confirmed the general knowledge on PRV pathogenesis. Several new findings and potential explanations for the observed age-dependent differences in virulence, however, were determined from the study of viral and cytokine mRNA expression at important sites of neuropathogenesis...
January 15, 2017: Journal of Virology
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