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Immunopathology of viral

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https://www.readbyqxmd.com/read/28077598/notch-ligand-delta-like-4-promotes-regulatory-t-cell-identity-in-pulmonary-viral-infection
#1
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...
January 11, 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
#2
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...
December 28, 2016: 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
Sara Verpoest, Brigitte Cay, Herman Favoreel, Nick De Regge
: Severity of clinical symptoms induced by pseudorabies virus (PRV) infection of its natural host is inversely related with the age of the pig. During this study, pigs of 2- and 15-week-old were inoculated with the PRV strain NIA3. This resulted in important clinical disease although associated morbidity and mortality were lower in older pigs. qPCR 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 sorted from the study of viral and cytokine mRNA expression at important sites of neuropathogenesis...
November 16, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27810927/scramblase-tmem16f-terminates-t-cell-receptor-signaling-to-restrict-t-cell-exhaustion
#13
Yu Hu, Ji Hyung Kim, Kangmin He, Qi Wan, Jessica Kim, Melanie Flach, Tom Kirchhausen, Andrea Vortkamp, Florian Winau
In chronic infection, T cells become hyporesponsive to antigenic stimulation to prevent immunopathology. Here, we show that TMEM16F is required to curb excessive T cell responses in chronic infection with virus. TMEM16F-deficient T cells are hyperactivated during the early phase of infection, exhibiting increased proliferation and cytokine production. Interestingly, this overactivation ultimately leads to severe T cell exhaustion and the inability of the host to control viral burden. Mechanistically, we identify TMEM16F as the dominant lipid scramblase in T lymphocytes that transports phospholipids across membranes...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27809306/cd169-macrophages-regulate-pd-l1-expression-via-type-i-interferon-and-thereby-prevent-severe-immunopathology-after-lcmv-infection
#14
Namir Shaabani, Vikas Duhan, Vishal Khairnar, Asmae Gassa, Rita Ferrer-Tur, Dieter Häussinger, Mike Recher, Gennadiy Zelinskyy, Jia Liu, Ulf Dittmer, Mirko Trilling, Stefanie Scheu, Cornelia Hardt, Philipp A Lang, Nadine Honke, Karl S Lang
Upon infection with persistence-prone virus, type I interferon (IFN-I) mediates antiviral activity and also upregulates the expression of programmed death ligand 1 (PD-L1), and this upregulation can lead to CD8(+) T-cell exhaustion. How these very diverse functions are regulated remains unknown. This study, using the lymphocytic choriomeningitis virus, showed that a subset of CD169(+) macrophages in murine spleen and lymph nodes produced high amounts of IFN-I upon infection. Absence of CD169(+) macrophages led to insufficient production of IFN-I, lower antiviral activity and persistence of virus...
November 3, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27807227/heterologous-immunity-and-persistent-murine-cytomegalovirus-infection
#15
Jenny W Che, Keith A Daniels, Liisa K Selin, Raymond M Welsh
: One's history of infections can affect the immune response to unrelated pathogens and influence disease outcome through the process of heterologous immunity. This can occur after acute viral infections, such as infections with lymphocytic choriomeningitis virus (LCMV) and vaccinia virus, where the pathogens are cleared, but it becomes a more complex issue in the context of persistent infections. In this study, murine cytomegalovirus (MCMV) was used as a persistent infection model to study heterologous immunity with LCMV...
January 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27698656/neutrophil-extracellular-traps-go-viral
#16
Günther Schönrich, Martin J Raftery
Neutrophils are the most numerous immune cells. Their importance as the first line of defense against bacterial and fungal pathogens is well described. In contrast, the role of neutrophils in controlling viral infections is less clear. Bacterial and fungal pathogens can stimulate neutrophils extracellular traps (NETs) in a process called NETosis. Although NETosis has previously been described as a special form of programmed cell death, there are forms of NET production that do not end with the demise of neutrophils...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27668213/the-quest-for-anti-inflammatory-and-anti-infective-biomaterials-in-clinical-translation
#17
REVIEW
May Griffith, Mohammad M Islam, Joel Edin, Georgia Papapavlou, Oleksiy Buznyk, Hirak K Patra
Biomaterials are now being used or evaluated clinically as implants to supplement the severe shortage of available human donor organs. To date, however, such implants have mainly been developed as scaffolds to promote the regeneration of failing organs due to old age or congenital malformations. In the real world, however, infection or immunological issues often compromise patients. For example, bacterial and viral infections can result in uncontrolled immunopathological damage and lead to organ failure. Hence, there is a need for biomaterials and implants that not only promote regeneration but also address issues that are specific to compromised patients, such as infection and inflammation...
2016: Frontiers in Bioengineering and Biotechnology
https://www.readbyqxmd.com/read/27631819/characterization-of-the-specificity-functionality-and-durability-of-host-t-cell-responses-against-the-full-length-hepatitis-e-virus
#18
Anthony Brown, John S Halliday, Leo Swadling, Richie G Madden, Richard Bendall, Jeremy G Hunter, James Maggs, Peter Simmonds, Donald B Smith, Louisa Vine, Cara McLaughlin, Jane Collier, David Bonsall, Katie Jeffery, Susanna Dunachie, Paul Klenerman, Jacques Izopet, Nassim Kamar, Harry R Dalton, Eleanor Barnes
: The interplay between host antiviral immunity and immunopathology during hepatitis E virus (HEV) infection determines important clinical outcomes. We characterized the specificity, functionality, and durability of host T-cell responses against the full-length HEV virus and assessed a novel "Quantiferon" assay for the rapid diagnosis of HEV infection. Eighty-nine volunteers were recruited from Oxford, Truro (UK), and Toulouse (France), including 44 immune-competent patients with acute HEV infection, 18 HEV-exposed immunosuppressed organ-transplant recipients (8 with chronic HEV), and 27 healthy volunteers...
December 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27623349/lymphotoxin-in-physiology-of-lymphoid-tissues-implication-for-antiviral-defense
#19
Ekaterina P Koroleva, Yang-Xin Fu, Alexei V Tumanov
Lymphotoxin (LT) is a member of the tumor necrosis factor (TNF) superfamily of cytokines which serves multiple functions, including the control of lymphoid organ development and maintenance, as well as regulation of inflammation and autoimmunity. Although the role of LT in organogenesis and maintenance of lymphoid organs is well established, the contribution of LT pathway to homeostasis of lymphoid organs during the immune response to pathogens is less understood. In this review, we highlight recent advances on the role of LT pathway in antiviral immune responses...
September 9, 2016: Cytokine
https://www.readbyqxmd.com/read/27611574/viral-infection-of-the-central-nervous-system-exacerbates-interleukin-10-receptor-deficiency-mediated-colitis-in-sjl-mice
#20
Ann-Kathrin Uhde, Vanessa Herder, Muhammad Akram Khan, Malgorzata Ciurkiewicz, Dirk Schaudien, René Teich, Stefan Floess, Wolfgang Baumgärtner, Jochen Huehn, Andreas Beineke
Theiler´s murine encephalomyelitis virus (TMEV)-infection is a widely used animal model for studying demyelinating disorders, including multiple sclerosis (MS). The immunosuppressive cytokine Interleukin (IL)-10 counteracts hyperactive immune responses and critically controls immune homeostasis in infectious and autoimmune disorders. In order to investigate the effect of signaling via Interleukin-10 receptor (IL-10R) in infectious neurological diseases, TMEV-infected SJL mice were treated with IL-10R blocking antibody (Ab) in the acute and chronic phase of the disease...
2016: PloS One
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