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Immunopathology of viral

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
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
A Brown, J S Halliday, L Swadling, R Madden, R Bendall, J G Hunter, J Maggs, P Simmonds, D B Smith, L Vine, C McLaughlin, J Collier, D Bonsall, K Jeffery, S J Dunachie, P Klenerman, J Izopet, N Kamar, H R Dalton, E Barnes
BACKGROUND AND AIMS: The interplay between host anti-viral immunity and immunopathology during Hepatitis E virus (HEV) infection determines important clinical outcomes. We characterised 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. METHODS: 89 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...
September 15, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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
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
Jessica R Spengler, Kerry J Lavender, Cynthia Martellaro, Aaron Carmody, Andreas Kurth, James G Keck, Greg Saturday, Dana P Scott, Stuart T Nichol, Kim J Hasenkrug, Christina F Spiropoulou, Heinz Feldmann, Joseph Prescott
The study of Ebola virus (EBOV) pathogenesis in vivo has been limited to nonhuman primate models or use of an adapted virus to cause disease in rodent models. Herein we describe wild-type EBOV (Makona variant) infection of mice engrafted with human hematopoietic CD34(+) stem cells (Hu-NSG™-SGM3 mice; hereafter referred to as SGM3 HuMice). SGM3 HuMice support increased development of myeloid immune cells, which are primary EBOV targets. In SGM3 HuMice, EBOV replicated to high levels, and disease was observed following either intraperitoneal or intramuscular inoculation...
October 15, 2016: Journal of Infectious Diseases
Martijn J Schuijs, Susanne Hartmann, Murray E Selkirk, Luke B Roberts, Peter J M Openshaw, Corinna Schnoeller
Respiratory Syncytial Virus (RSV) is a major pathogen causing low respiratory tract disease (bronchiolitis), primarily in infants. Helminthic infections may alter host immune responses to both helminths and to unrelated immune triggers. For example, we have previously shown that filarial cystatin (AvCystatin/Av17) ameliorates allergic airway inflammation. However, helminthic immunomodulators have so far not been tested in virus-induced disease. We now report that AvCystatin prevents Th2-based immunopathology in vaccine-enhanced RSV lung inflammation, a murine model for bronchiolitis...
2016: PloS One
Stephanie Johnstone, Jekaterina Barsova, Isabel Campos, Arthur R Frampton
Equine herpesvirus myeloencephalopathy (EHM), a disease caused by equine herpesvirus type 1 (EHV-1), is characterized by severe inflammation, thrombosis, and hypoxia in central nervous system (CNS) endothelial cells, which can result in a spectrum of clinical signs including urinary incontinence, ataxia, and paralysis. Strains of EHV-1 that contain a single point mutation within the viral DNA polymerase (nucleotide A2254>G2254: amino acid N752→D752) are isolated from EHM afflicted horses at higher frequencies than EHV-1 strains that do not harbor this mutation...
August 30, 2016: Veterinary Microbiology
Sophia Davidson, Teresa M McCabe, Stefania Crotta, Hans Henrik Gad, Edith M Hessel, Soren Beinke, Rune Hartmann, Andreas Wack
Influenza A virus (IAV)-induced severe disease is characterized by infected lung epithelia, robust inflammatory responses and acute lung injury. Since type I interferon (IFNαβ) and type III interferon (IFNλ) are potent antiviral cytokines with immunomodulatory potential, we assessed their efficacy as IAV treatments. IFNλ treatment of IAV-infected Mx1-positive mice lowered viral load and protected from disease. IFNα treatment also restricted IAV replication but exacerbated disease. IFNα treatment increased pulmonary proinflammatory cytokine secretion, innate cell recruitment and epithelial cell death, unlike IFNλ-treatment...
2016: EMBO Molecular Medicine
Amanda L Gill, Samantha A Green, Shahed Abdullah, Cecile Le Saout, Stefania Pittaluga, Hui Chen, Refika Turnier, Jeffrey Lifson, Steven Godin, Jing Qin, Michael C Sneller, Jean-Marie Cuillerot, Helen Sabzevari, H Clifford Lane, Marta Catalfamo
OBJECTIVE: The programed death-1 (PD1)/programed death-ligand 1 (PD-L1) pathway plays a critical role in balancing immunity and host immunopathology. During chronic HIV/SIV infection, there is persistent immune activation accompanied by accumulation of virus-specific cells with terminally differentiated phenotypes and expression of regulatory receptors such as PD1. These observations led us to hypothesize that the PD1/PD-L1 pathway contributes to the functional dysregulation and ineffective viral control, and its blockade may be a potential immunotherapeutic target...
October 23, 2016: AIDS
Pushpa Pandiyan, Souheil-Antoine Younes, Susan Pereira Ribeiro, Aarthi Talla, David McDonald, Natarajan Bhaskaran, Alan D Levine, Aaron Weinberg, Rafick P Sekaly
Residual mucosal inflammation along with chronic systemic immune activation is an important feature in individuals infected with human immunodeficiency virus (HIV), and has been linked to a wide range of co-morbidities, including malignancy, opportunistic infections, immunopathology, and cardiovascular complications. Although combined antiretroviral therapy (cART) can reduce plasma viral loads to undetectable levels, reservoirs of virus persist, and increased mortality is associated with immune dysbiosis in mucosal lymphoid tissues...
2016: Frontiers in Immunology
Jia Xue, Xiaoxu Fan, Jing Yu, Shouping Zhang, Jin Xiao, Yanxin Hu, Ming Wang
Highly pathogenic avian influenza virus (HPAIV) H5N1 is a highly contagious virus that can cause acute respiratory infections and high human fatality ratio due to excessive inflammatory response. Short-term heat shock, as a stressful condition, could induce the expression of heat shock proteins that function as molecular chaperones to protect cells against multiple stresses. However, the protective effect of short-term heat shock in influenza infection is far from being understood. In this study, mice were treated at 39°C for 4 h before being infected with HPAIV H5N1...
2016: Frontiers in Microbiology
Eui-Cheol Shin, Pil Soo Sung, Su-Hyung Park
Hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are responsible for most cases of viral hepatitis. Infection by each type of virus results in a different typical natural disease course and clinical outcome that are determined by virological and immunological factors. HCV tends to establish a chronic persistent infection, whereas HAV does not. HBV is effectively controlled in adults, although it persists for a lifetime after neonatal infection. In this Review, we discuss the similarities and differences in immune responses to and immunopathogenesis of HAV, HBV and HCV infections, which may explain the distinct courses and outcomes of each hepatitis virus infection...
August 2016: Nature Reviews. Immunology
Myung-Soo Choi, Jinyuk Heo, Chae-Min Yi, Junsu Ban, Noh-Jin Lee, Na-Rae Lee, Sang Won Kim, Nam-Jung Kim, Kyung-Soo Inn
Respiratory syncytial virus (RSV) and influenza A virus are leading causes of acute lower respiratory infectious disease. Respiratory diseases caused by RSV and influenza A virus result in serious economic burden and life-threatening disease for immunocompromised people. With the revelation that p38 mitogen-activated protein kinase (MAPK) activity in host cells is crucial for infection and replication of RSV and influenza A virus, inhibition of p38 MAPK activity has been suggested as a potential antiviral therapeutic strategy...
August 26, 2016: Biochemical and Biophysical Research Communications
Bonnie van Wilgenburg, Iris Scherwitzl, Edward C Hutchinson, Tianqi Leng, Ayako Kurioka, Corinna Kulicke, Catherine de Lara, Suzanne Cole, Sirijitt Vasanawathana, Wannee Limpitikul, Prida Malasit, Duncan Young, Laura Denney, Michael D Moore, Paolo Fabris, Maria Teresa Giordani, Ye Htun Oo, Stephen M Laidlaw, Lynn B Dustin, Ling-Pei Ho, Fiona M Thompson, Narayan Ramamurthy, Juthathip Mongkolsapaya, Christian B Willberg, Gavin R Screaton, Paul Klenerman
Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize bacterial ligands. Here, we demonstrate that MAIT cells are also activated during human viral infections in vivo. MAIT cells activation was observed during infection with dengue virus, hepatitis C virus and influenza virus. This activation-driving cytokine release and Granzyme B upregulation-is TCR-independent but dependent on IL-18 in synergy with IL-12, IL-15 and/or interferon-α/β. IL-18 levels and MAIT cell activation correlate with disease severity in acute dengue infection...
2016: Nature Communications
Jan-Hendrik Kozik, Tanja Trautmann, Antonella Carambia, Max Preti, Marc Lütgehetmann, Till Krech, Christiane Wiegard, Joerg Heeren, Johannes Herkel
TREM1 (Triggering Receptor Expressed on Myeloid Cells 1) is a pro-inflammatory receptor expressed by phagocytes, which can also be released as a soluble molecule (sTREM1). The roles of TREM1 and sTREM1 in liver infection and inflammation are not clear. Here we show that patients with hepatitis B virus (HBV) or hepatitis C virus (HCV) infection manifest elevated serum levels of sTREM1. In mice, experimental viral hepatitis induced by infection with Lymphocytic Choriomeningitis Virus (LCMV)-WE was likewise associated with increased sTREM1 in serum and urine, and with increased TREM1 and its associated adapter molecule DAP12 in the liver...
2016: Scientific Reports
Jennifer M Loftis, Jonathan Taylor, Hans-Peter Raué, Mark K Slifka, Elaine Huang
Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans...
October 1, 2016: Behavioural Brain Research
Jun Meng, Xingguang Liu, Peng Zhang, Dong Li, Sheng Xu, Qingqing Zhou, Meng Guo, Wanwan Huai, Xiang Chen, Quanxing Wang, Nan Li, Xuetao Cao
Type I IFN production is tightly controlled by host to generate efficient viral clearance without harmful immunopathology or induction of autoimmune disorders. Epigenetic regulation of type I IFN production in innate immunity and inflammatory disorders remains to be fully understood. Several tumor suppressors have been shown to regulate immune response and inflammation. However, the non-classical functions of tumor suppressors in innate immunity and inflammatory diseases need further identification. Here we report retinoblastoma protein (Rb) deficiency selectively enhanced TLR- and virus-triggered production of IFN-β which thus induced more IFN-α generation in the later phase of innate stimuli, but had no effect on the production of TNF, IL-6 and early phase IFN-α in macrophages...
September 2016: Journal of Autoimmunity
Jin Hyoung Kim, Ajit Mahadev Patil, Jin Young Choi, Seong Bum Kim, Erdenebileg Uyangaa, Ferdaus Mohd Altaf Hossain, Sang-Youel Park, John Hwa Lee, Koanhoi Kim, Seong Kug Eo
Japanese encephalitis virus (JEV) is a re-emerging zoonotic flavivirus that poses an increasing threat to global health and welfare due to rapid changes in climate and demography. Although the CCR2-CCL2 axis plays an important role in trafficking CD11b(+) Ly-6C(hi) monocytes to regulate immunopathological diseases, little is known about their role in monocyte trafficking during viral encephalitis caused by JEV infection. Here, we explored the role of CCR2 and its ligand CCL2 in JE caused by JEV infection using CCR2- and CCL2-ablated murine models...
October 2016: Immunology
John J Erickson, Meredith C Rogers, Sharon J Tollefson, Kelli L Boyd, John V Williams
Viruses are frequent causes of lower respiratory infection (LRI). Programmed cell death-1 (PD-1) signaling contributes to pulmonary CD8(+) T cell (TCD8) functional impairment during acute viral LRI, but the role of TCD8 impairment in viral clearance and immunopathology is unclear. We now find that human metapneumovirus infection induces virus-specific lung TCD8 that fail to produce effector cytokines or degranulate late postinfection, with minimally increased function even in the absence of PD-1 signaling. Impaired lung TCD8 upregulated multiple inhibitory receptors, including PD-1, lymphocyte activation gene 3 (LAG-3), T cell Ig mucin 3, and 2B4...
July 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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