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https://www.readbyqxmd.com/read/27926943/the-mouse-cytomegalovirus-gene-m42-targets-surface-expression-of-the-protein-tyrosine-phosphatase-cd45-in-infected-macrophages
#1
Nadine Thiel, Kirsten A Keyser, Niels A W Lemmermann, Jennifer D Oduro, Karen Wagner, Carina Elsner, Anne Halenius, Tihana Lenac Roviš, Melanie M Brinkmann, Stipan Jonjić, Luka Cicin-Sain, Martin Messerle
The receptor-like protein tyrosine phosphatase CD45 is expressed on the surface of cells of hematopoietic origin and has a pivotal role for the function of these cells in the immune response. Here we report that following infection of macrophages with mouse cytomegalovirus (MCMV) the cell surface expression of CD45 is drastically diminished. Screening of a set of MCMV deletion mutants allowed us to identify the viral gene m42 of being responsible for CD45 down-modulation. Moreover, expression of m42 independent of viral infection upon retroviral transduction of the RAW264...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926941/type-1-interferons-and-nk-cells-limit-murine-cytomegalovirus-escape-from-the-lymph-node-subcapsular-sinus
#2
Helen E Farrell, Kimberley Bruce, Clara Lawler, Rhonda D Cardin, Nicholas J Davis-Poynter, Philip G Stevenson
Cytomegaloviruses (CMVs) establish chronic, systemic infections. Peripheral infection spreads via lymph nodes, which are also a focus of host defence. Thus, this is a point at which systemic infection spread might be restricted. Subcapsular sinus macrophages (SSM) captured murine CMV (MCMV) from the afferent lymph and poorly supported its replication. Blocking the type I interferon (IFN-I) receptor (IFNAR) increased MCMV infection of SSM and of the fibroblastic reticular cells (FRC) lining the subcapsular sinus, and accelerated viral spread to the spleen...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926931/microbial-translocation-and-inflammation-occur-in-hyperacute-immunodeficiency-virus-infection-and-compromise-host-control-of-virus-replication
#3
Adam J Ericsen, Michael Lauck, Mariel S Mohns, Sarah R DiNapoli, James P Mutschler, Justin M Greene, Jason T Weinfurter, Gabrielle Lehrer-Brey, Trent M Prall, Samantha M Gieger, Connor R Buechler, Kristin A Crosno, Eric J Peterson, Matthew R Reynolds, Roger W Wiseman, Benjamin J Burwitz, Jacob D Estes, Jonah B Sacha, Thomas C Friedrich, Jason M Brenchley, David H O'Connor
Within the first three weeks of human immunodeficiency virus (HIV) infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS), there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV) infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926930/cytomegalovirus-specific-il-10-producing-cd4-t-cells-are-governed-by-type-i-ifn-induced-il-27-and-promote-virus-persistence
#4
Mathew Clement, Morgan Marsden, Maria A Stacey, Juneid Abdul-Karim, Silvia Gimeno Brias, Diana Costa Bento, Martin J Scurr, Peter Ghazal, Casey T Weaver, Gianluca Carlesso, Simon Clare, Simon A Jones, Andrew Godkin, Gareth W Jones, Ian R Humphreys
CD4+ T cells support host defence against herpesviruses and other viral pathogens. We identified that CD4+ T cells from systemic and mucosal tissues of hosts infected with the β-herpesviridae human cytomegalovirus (HCMV) or murine cytomegalovirus (MCMV) express the regulatory cytokine interleukin (IL)-10. IL-10+CD4+ T cells co-expressed TH1-associated transcription factors and chemokine receptors. Mice lacking T cell-derived IL-10 elicited enhanced antiviral T cell responses and restricted MCMV persistence in salivary glands and secretion in saliva...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926929/functional-and-evolutionary-analyses-identify-proteolysis-as-a-general-mechanism-for-nlrp1-inflammasome-activation
#5
Joseph Chavarría-Smith, Patrick S Mitchell, Alvin M Ho, Matthew D Daugherty, Russell E Vance
Inflammasomes are cytosolic multi-protein complexes that initiate immune responses to infection by recruiting and activating the Caspase-1 protease. Human NLRP1 was the first protein shown to form an inflammasome, but its physiological mechanism of activation remains unknown. Recently, specific variants of mouse and rat NLRP1 were found to be activated upon N-terminal cleavage by the anthrax lethal factor protease. However, agonists for other NLRP1 variants, including human NLRP1, are not known, and it remains unclear if they are also activated by proteolysis...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27926921/schistosoma-mansoni-infection-can-jeopardize-the-duration-of-protective-levels-of-antibody-responses-to-immunizations-against-hepatitis-b-and-tetanus-toxoid
#6
Diana K Riner, Eric M Ndombi, Jennifer M Carter, Amos Omondi, Nupur Kittur, Emmy Kavere, Harrison K Korir, Briana Flaherty, Diana Karanja, Daniel G Colley
BACKGROUND: Schistosomiasis is a disease of major public health importance in sub-Saharan Africa. Immunoregulation begins early in schistosome infection and is characterized by hyporesponsiveness to parasite and bystander antigens, suggesting that a schistosome infection at the time of immunization could negatively impact the induction of protective vaccine responses. This study examined whether having a Schistosoma mansoni infection at the time of immunization with hepatitis B and tetanus toxoid (TT) vaccines impacts an individual's ability to achieve and maintain protective antibody levels against hepatitis B surface antigen or TT...
December 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27926862/vav-proteins-are-key-regulators-of-card9-signaling-for-innate-antifungal-immunity
#7
Susanne Roth, Hanna Bergmann, Martin Jaeger, Assa Yeroslaviz, Konstantin Neumann, Paul-Albert Koenig, Clarissa Prazeres da Costa, Lesley Vanes, Vinod Kumar, Melissa Johnson, Mauricio Menacho-Márquez, Bianca Habermann, Victor L Tybulewicz, Mihai Netea, Xosé R Bustelo, Jürgen Ruland
Fungal infections are major causes of morbidity and mortality, especially in immunocompromised individuals. The innate immune system senses fungal pathogens through Syk-coupled C-type lectin receptors (CLRs), which signal through the conserved immune adaptor Card9. Although Card9 is essential for antifungal defense, the mechanisms that couple CLR-proximal events to Card9 control are not well defined. Here, we identify Vav proteins as key activators of the Card9 pathway. Vav1, Vav2, and Vav3 cooperate downstream of Dectin-1, Dectin-2, and Mincle to engage Card9 for NF-κB control and proinflammatory gene transcription...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926861/immunometabolic-pathways-in-bcg-induced-trained-immunity
#8
Rob J W Arts, Agostinho Carvalho, Claudia La Rocca, Carla Palma, Fernando Rodrigues, Ricardo Silvestre, Johanneke Kleinnijenhuis, Ekta Lachmandas, Luís G Gonçalves, Ana Belinha, Cristina Cunha, Marije Oosting, Leo A B Joosten, Giuseppe Matarese, Reinout van Crevel, Mihai G Netea
The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such as monocytes, a process termed trained immunity. Here, we show that BCG induction of trained immunity in monocytes is accompanied by a strong increase in glycolysis and, to a lesser extent, glutamine metabolism, both in an in-vitro model and after vaccination of mice and humans...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926855/temporally-programmed-cd8%C3%AE-dc-activation-enhances-combination-cancer-immunotherapy
#9
Alice Tzeng, Monique J Kauke, Eric F Zhu, Kelly D Moynihan, Cary F Opel, Nicole J Yang, Naveen Mehta, Ryan L Kelly, Gregory L Szeto, Willem W Overwijk, Darrell J Irvine, K Dane Wittrup
Numerous synergistic cancer immunotherapy combinations have been identified, but the effects of relative dose timing are rarely considered. In established syngeneic mouse tumor models, we found that staggering interferon-α (IFNα) administration after, rather than before or simultaneously with, serum-persistent interleukin-2 (IL-2) and tumor-specific antibody significantly increased long-term survival. Successful combination therapy required IFNα-induced activation of cross-presenting CD8α(+) dendritic cells (DCs) following the release of antigenic tumor debris by the IL-2- and antibody-mediated immune response...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926826/potential-of-a-bpv1-l1-vlp-vaccine-to-prevent-bpv1-or-bpv2-induced-pseudo-sarcoid-formation-and-safety-and-immunogenicity-of-ecpv2-l1-vlps-in-the-horse
#10
Edmund K Hainisch, Hans Abel-Reichwald, Saeed Shafti-Keramat, Barbara Pratscher, Annunziata Corteggio, Giuseppe Borzacchiello, Maria Wetzig, Christoph Jindra, Alexander Tichy, Reinhard Kirnbauer, Sabine Brandt
We have previously shown that immunization of horses with BPV1 L1 virus-like particles (VLP) is safe and highly immunogenic, and that bovine papillomavirus types 1 and 2 (BPV1, BPV2) are closely related serotypes. Here we evaluated the protective potential of a BPV1 L1 VLP vaccine against experimental BPV1 and BPV2 challenge, and studied the safety and immunogenicity of a bivalent EcPV2/BPV1 L1 VLP vaccine. Fourteen healthy horses were immunized with BPV1 L1 VLPs (100 µg/injection) plus adjuvant on days 0 and 28, whilst seven remained unvaccinated...
December 7, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27926825/mycobacterium-malmesburyense-sp-nov-a-novel-non-tuberculous-mycobacterium-species-revealed-by-multiple-gene-sequence-characterization
#11
Nomakorinte Gcebe, Victor Rutten, Nicolaas Gey van Pittius, Brendon Naicker, Anita Michel
Non-tuberculous mycobacteria (NTM) are ubiquitous in the environment and an increasing number of NTM species have been isolated and characterized from both humans and animals, highlighting the zoonotic potential of these bacteria. Host exposure to NTM may impact on cross-reactive immune responsiveness which may affect diagnosis of bovine tuberculosis and may also play a role in the variability of the efficacy of Mycobacterium bovis BCG vaccination against tuberculosis. In this study we characterized 10 NTM isolates originating from water, soil, nasal swabs of cattle and African buffalo as well as bovine tissue samples...
December 5, 2016: International Journal of Systematic and Evolutionary Microbiology
https://www.readbyqxmd.com/read/27926762/association-of-arterial-and-lymph-node-inflammation-with-distinct-inflammatory-pathways-in-human-immunodeficiency-virus-infection
#12
Ahmed Tawakol, Amorina Ishai, Danny Li, Richard A P Takx, Sophia Hur, Yannick Kaiser, Miguel Pampaloni, Adam Rupert, Denise Hsu, Irini Sereti, Rémi Fromentin, Nicolas Chomont, Peter Ganz, Steven G Deeks, Priscilla Y Hsue
Importance: Human immunodeficiency virus (HIV) infection is associated with a high risk of cardiovascular disease and increased arterial inflammation. In HIV, inflammation is also increased within lymph nodes (LNs), tissues known to harbor the virus even among treated and suppressed individuals. Objective: To test the hypothesis that arterial inflammation is linked to HIV disease activity and to inflammation within HIV-infected tissues (LNs). Design, Setting, and Participants: For this case-control study, participants were recruited from the SCOPE (Observational Study of the Consequences of the Protease Inhibitor Era) cohort, a clinic-based cohort of individuals receiving care at San Francisco General Hospital and the San Francisco Veteran's Affairs Medical Center...
December 7, 2016: JAMA Cardiology
https://www.readbyqxmd.com/read/27926729/intracellular-allosteric-antagonism-of-the-ccr9-receptor
#13
Christine Oswald, Mathieu Rappas, James Kean, Andrew S Doré, James C Errey, Kirstie Bennett, Francesca Deflorian, John A Christopher, Ali Jazayeri, Jonathan S Mason, Miles Congreve, Robert M Cooke, Fiona H Marshall
Chemokines and their G-protein-coupled receptors play a diverse role in immune defence by controlling the migration, activation and survival of immune cells. They are also involved in viral entry, tumour growth and metastasis and hence are important drug targets in a wide range of diseases. Despite very significant efforts by the pharmaceutical industry to develop drugs, with over 50 small-molecule drugs directed at the family entering clinical development, only two compounds have reached the market: maraviroc (CCR5) for HIV infection and plerixafor (CXCR4) for stem-cell mobilization...
December 7, 2016: Nature
https://www.readbyqxmd.com/read/27926613/optimal-multidisciplinary-treatment-of-oral-cavity-mucosal-melanoma-outcome-analysis-in-a-case-series
#14
Francesco Perri, Salvatore Pisconti, Matteo Favia, Giuseppina Della Vittoria Scarpati, Manuel Conson, Mario Giuliano, Franco Ionna, Francesco Longo, Bonamonte Domenico, Eugenio Maiorano, Gianfranco Favia
Oral cavity mucosal melanomas (OCMM) represent only 3% of all malignant melanomas. Surgery is the mainstay of treatments and it is often followed by adjuvant radiotherapy. The role of adjuvant immunotherapy and/or chemotherapy is still debated and to date neither treatment is routinely used. From January 1990 to January 2010, we have collected from our database data of 20 patients with a histologically proven diagnosis of OCMM. Upfront surgery, followed by adjuvant radiotherapy was performed in 16/20 (80%) patients...
December 6, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27926581/diagnostic-value-of-platelet-indices-and-bone-marrow-megakaryocytic-parameters-in-immune-thrombocytopenic-purpura
#15
Yue-Ting Tang, Ping He, Ya-Zhen Li, Huan-Zhu Chen, Xiao-Lan Chang, Qing-Dong Xie, Xiao-Yang Jiao
Platelet indices could mirror megakaryopoietic activity in immune thrombocytopenic purpura (ITP), but its specificity and sensitivity need to be studied. The diagnostic performance of platelet indices was analyzed by receiver-operating characteristic curves, and the probability of true positive (sensitivity) and true negative (specificity) in predicting ITP, myelodysplasia, or controls was determined. Mean platelet volume (MPV) was higher, whereas plateletcrit (PCT) was significantly lower in ITP than in myelodysplasia and controls...
December 6, 2016: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/27926546/the-effect-of-chronic-kidney-disease-on-t-cell-alloimmunity
#16
Pamela D Winterberg, Mandy L Ford
PURPOSE OF REVIEW: Altered differentiation and activation of T-cell subsets occur in patients with chronic kidney disease (CKD), but the impact on graft rejection and protective immunity during transplantation are not fully understood. RECENT FINDINGS: Patients with CKD have decreased frequency of naïve T cells, accumulation of activated, terminally differentiated memory cells, and skewed regulatory versus T helper 17 ratio. Naïve and memory T-cell subsets do not appear to improve following kidney transplantation...
December 6, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27926545/immune-responses-to-bioengineered-organs
#17
Jordi Ochando, Dominique Charron, Pedro M Baptista, Basak E Uygun
PURPOSE OF REVIEW: Organ donation in the United States registered 9079 deceased organ donors in 2015. This high percentage of donations allowed organ transplantation in 29 851 recipients. Despite increasing numbers of transplants performed in comparison with previous years, the numbers of patients that are in need for a transplant increase every year at a higher rate. This reveals that the discrepancy between the demand and availability of organs remains fundamental problem in organ transplantation...
December 6, 2016: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/27926535/high-salt-diet-stimulates-gut-th17-response-and-exacerbates-tnbs-induced-colitis-in-mice
#18
Yingfeng Wei, Chong Lu, Jianing Chen, Guangying Cui, Lin Wang, Tianming Yu, Yue Yang, Wei Wu, Yulong Ding, Lanjuan Li, Toshimitsu Uede, Zhi Chen, Hongyan Diao
This study focuses on characterizing the effect of a high salt diet (HSD) on intestinal immunity and the risk of inflammatory bowel diseases (IBD). We found that mice on a HSD had an increased frequency of IL-17A producing cells in the intestinal lamina propria (LP) compared to mice on a normal diet (ND). Furthermore, most intestinal IL-17A producing cells were CD4+TCRβ+ cells. A HSD increased the LP T helper 17 (Th17) responses in both the small and large intestines but did not increase the Th17 response of other gut-associated lymphoid organ...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926522/il-10-expression-defines-an-immunosuppressive-dendritic-cell-population-induced-by-antitumor-therapeutic-vaccination
#19
Diana Llopiz, Marta Ruiz, Stefany Infante, Lorea Villanueva, Leyre Silva, Sandra Hervas-Stubbs, Diego Alignani, Elizabeth Guruceaga, Juan J Lasarte, Pablo Sarobe
Vaccination induces immunostimulatory signals that are often accompanied by regulatory mechanisms such as IL-10, which control T-cell activation and inhibit vaccine-dependent antitumor therapeutic effect. Here we characterized IL-10-producing cells in different tumor models treated with therapeutic vaccines. Although several cell subsets produced IL-10 irrespective of treatment, an early vaccine-dependent induction of IL-10 was detected in dendritic cells (DC). IL-10 production defined a DC population characterized by a poorly mature phenotype, lower expression of T-cell stimulating molecules and upregulation of PD-L1...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926518/higher-programmed-cell-death-1-ligand-1-pd-l1-mrna-level-in-clear-cell-renal-cell-carcinomas-is-associated-with-a-favorable-outcome-due-to-the-active-immune-responses-in-tumor-tissues
#20
Xiang-Hui Ning, Yan-Qing Gong, Shi-Ming He, Teng Li, Jiang-Yi Wang, Shuang-He Peng, Jin-Chao Chen, Jia-Yuan Liu, Nie-Nie Qi, Ying-Lu Guo, Kan Gong
Renal cell carcinoma is one of the most common urological tumors. The role of programmed cell death 1 ligand 1 (PD-L1) in renal cell carcinomas in predicting outcome of the patients is yet unclear. We analyzed the clinical and RNA-seq data of 522 kidney clear cell cancer, 259 kidney papillary cell carcinoma and 66 kidney chromophobe patients from The Cancer Genome Atlas (TCGA) database. In kidney clear cell cancer patients with high PD-L1 mRNA level and low PD-L1 mRNA level in tumors, the median overall survival periods were 45...
December 1, 2016: Oncotarget
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