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Immunology and Cell Biology

Kyle Malone, Sylvie Amu, Anne C Moore, Christian Waeber
Stroke is a major cause of morbidity and mortality worldwide. Despite the intensive search for new therapies, hundreds of agents targeting various pathophysiological mechanisms have failed clinical trials, and the thrombolytic agent tissue plasminogen activator is currently the only FDA-approved medication for the treatment of acute ischaemic stroke (AIS). The immune system is involved in all stages of stroke, from the pathogenesis of risk factors to neurotoxicity, to tissue remodelling and repair. There is a bi-directional interaction between the brain and the immune system, with stroke-induced immunosuppression and subsequent infection a principal source of patient mortality...
July 19, 2018: Immunology and Cell Biology
Natalie J Bitto, Paul J Baker, Jennifer K Dowling, Georgie Wray-McCann, Amanda De Paoli, Le Son Tran, Pak Ling Leung, Katryn J Stacey, Ashley Mansell, Seth L Masters, Richard L Ferrero
Outer membrane vesicles (OMVs) are constitutively produced by Gram-negative bacteria both in vivo and in vitro. These lipid-bound structures carry a range of immunogenic components derived from the parent cell, which are transported into host target cells and activate the innate immune system. Recent advances in the field have shed light on some of the multifaceted roles of OMVs in host-pathogen interactions. In this study, we investigated the ability of OMVs from two clinically important pathogens, Pseudomonas aeruginosa and Helicobacter pylori, to activate canonical and non-canonical inflammasomes...
July 12, 2018: Immunology and Cell Biology
Anne C La Flamme
No abstract text is available yet for this article.
July 10, 2018: Immunology and Cell Biology
Rachael Keating, Melissa Y Morris, Wen Yue, Cory E Reynolds, Tarsha L Harris, Scott A Brown, Peter C Doherty, Paul G Thomas, Maureen A McGargill
Current influenza A virus (IAV) vaccines stimulate antibody responses that are directed against variable regions of the virus, and are therefore ineffective against divergent strains. As CD8+ T cells target the highly conserved, internal IAV proteins, they have the potential to increase heterosubtypic immunity. Early T cell priming events influence lasting memory, which is required for long-term protection. However, the early responding, IAV-specific cells are difficult to monitor due to their low frequencies...
July 4, 2018: Immunology and Cell Biology
Jennifer Bermick, Matthew Schaller
No abstract text is available yet for this article.
June 21, 2018: Immunology and Cell Biology
Stuart J Cook, Quintin Lee, Alex C H Wong, Benjamin C Spann, Jonathan N Vincent, Justin J L Wong, Andreas Schlitzer, Mark D Gorrell, Wolfgang Weninger, Ben Roediger
Conventional dendritic cells (cDCs) are continuously replenished by bone marrow-derived precursors called pre-DCs, which traffic through the blood to peripheral tissues. Pre-DCs are a heterogeneous population that includes cDC subset-committed progenitors, namely pre-cDC1 and pre-cDC2, which give rise to mature cDC1 and cDC2, respectively. However, the molecular cues regulating pre-cDC1 versus pre-cDC2 trafficking towards peripheral sites during homeostasis and disease remain elusive. Here, we report that pre-cDC1 but not pre-cDC2 express the T helper type 1-associated chemokine receptor CXCR3...
June 19, 2018: Immunology and Cell Biology
Kosuke Zenke, Masashi Muroi, Ken-Ichi Tanamoto
The signal transducer and activator of transcription 1 (STAT1), a pivotal transcription factor in Janus kinase (JAK)-STAT signaling, regulates the expression of a wide range of immune-related genes, including interferon (IFN) regulatory factor 1 (IRF1). In this study, we found that IRF1 could induce STAT1 phosphorylation and in turn STAT1 activation. When IRF1 was transiently expressed in HEK293 cells, STAT1 phosphorylated at Y701, dimerized and bound to an oligonucleotide containing a gamma-activated sequence (GAS) derived from the IRF1 promoter...
June 12, 2018: Immunology and Cell Biology
Abdulla A-B Badawy
Tumoral immune escape is an obstacle to successful cancer therapy. Tryptophan (Trp) metabolites along the kynurenine pathway induce immunosuppression involving apoptosis of effector immune cells, which tumors use to escape an immune response. Production of these metabolites is initiated by indoleamine 2,3-dioxygenase (IDO1). IDO1 inhibitors, however, do not always overcome the immune escape and another enzyme expressed in tumors, Trp 2,3-dioxygenase (TDO2), has been suggested as the reason. However, without Trp, tumors cannot achieve an immune escape through either enzyme...
June 10, 2018: Immunology and Cell Biology
Casper Marsman, Fanny Lafouresse, Yang Liao, Tracey M Baldwin, Lisa A Mielke, Yifang Hu, Matthias Mack, Paul J Hertzog, Carolyn A de Graaf, Wei Shi, Joanna R Groom
Plasmacytoid dendritic cells (pDCs) play a critical role in bridging the innate and adaptive immune systems. pDCs are specialized type I interferon (IFN) producers, which has implicated them as initiators of autoimmune pathogenesis. However, little is known about the downstream effectors of type I IFN signaling that amplify autoimmune responses. Here, we have used a chemokine reporter mouse to determine the CXCR3 ligand responses in DCs subsets. Following TLR7 stimulation, conventional type 1 and type 2 DCs (cDC1 and cDC2, respectively) uniformly upregulate CXCL10...
June 5, 2018: Immunology and Cell Biology
Chie Watanabe, Geraldine L Shu, Natalia V Giltiay, Edward A Clark
The caspase (Casp) family of proteases regulate both lymphocyte apoptosis and activation. Here, we show that Casp6 regulates early B-cell development. One-week-old Casp6 knockout (Casp6 KO) mice have significantly more splenic B-cell subsets than wild-type (WT) mice. Adult Casp6 KO mice have normal levels of total splenic B cells but have increased numbers of B1a B cells and CD43+ "transitional" or splenic red pulp (RP) B cells. These results suggested that Casp6 may function to control B-cell numbers under nonhomeostatic conditions and during B-cell development...
June 4, 2018: Immunology and Cell Biology
Daniel G Pellicci, Paul Klenerman
No abstract text is available yet for this article.
June 2, 2018: Immunology and Cell Biology
Ramon M Eichenberger, Javier Sotillo, Alex Loukas
Helminth parasites (worms) have evolved a vast array of strategies to manipulate their vertebrate hosts. Extracellular vesicles (EVs) are secreted by all helminth species investigated thus far, and their salient roles in parasite-host interactions are being revealed. Parasite EVs directly interact with various cell types from their hosts, including immune cells, and roles for their molecular cargo in both regulation and promotion of inflammation in the host have been reported. Despite the growing body of literature on helminth EVs, limited availability of genetic manipulation tools for helminth research has precluded detailed investigation of specific molecular interactions between parasite EVs and host target cells...
May 29, 2018: Immunology and Cell Biology
Dario A Leone, Andrew J Rees, Renate Kain
Extracellular vesicles, released from cells, are important for intercellular communication. They are heterogeneous but fall into two broad categories based on origin and function: microvesicles formed by outward budding from the plasma membrane; and exosomes that originate as intraluminal vesicles in multivesicular endosomes that fuse with the plasma membrane to release them. Extracellular vesicles generally and exosomes in particular have powerful effects on specific immune responses, and recent advances highlight their potential therapeutic uses...
May 24, 2018: Immunology and Cell Biology
Paola Cura Daball, Monica Sofia Ventura Ferreira, Sandra Ammann, Christian Klemann, Myriam R Lorenz, Ursula Warthorst, Timothy Ronan Leahy, Niall Conlon, Justin Roche, Pere Soler-Palacín, Marina Garcia-Prat, Ilka Fuchs, Sebastian Fuchs, Fabian Beier, Tim H Brümmendorf, Carsten Speckmann, Peter Olbrich, Olaf Neth, Klaus Schwarz, Stephan Ehl, Anne Rensing-Ehl
Premature T-cell immunosenescence with CD57+ CD8+ T-cell accumulation has been linked to immunodeficiency and autoimmunity in primary immunodeficiencies including activated PI3 kinase delta syndrome (APDS). To address whether CD57 marks the typical senescent T-cell population seen in adult individuals or identifies a distinct population in APDS, we compared CD57+ CD8+ T cells from mostly pediatric APDS patients to those of healthy adults with similarly prominent senescent T cells. CD57+ CD8+ T cells from APDS patients were less differentiated with more CD27+ CD28+ effector memory T cells showing increased PD1 and Eomesodermin expression...
May 23, 2018: Immunology and Cell Biology
Sreeparna Chakraborty, Pushpak Bhattacharjee, Abir K Panda, Kirti Kajal, Sayantan Bose, Gaurisankar Sa
CD8+ T-regulatory cells are progressively emerging as crucial components of immune system. The previous report suggests the presence of FOXP3-positive CD8+ Treg cells, similar to CD4+ Tregs, in cancer patients which produce high levels of IL10 and TGFβ for its immunosuppressive activities. At an early stage of tumor development, we have identified a subset of FOXP3-negative CD8+ CD25+ KIR+ CD127- a Treg-like subset which is essentially IFNγ-positive. However, this early induced CD8+ CD25+ CD127- T cell subset certainly distinct from the IFNγ+ CD8+ T-effecter cells...
May 16, 2018: Immunology and Cell Biology
Siobhan Crittenden, Ashleigh Cheyne, Alexander Adams, Thorsten Forster, Calum T Robb, Jennifer Felton, Gwo-Tzer Ho, Dominik Ruckerl, Adriano G Rossi, Stephen M Anderton, Peter Ghazal, Jack Satsangi, Sarah E Howie, Chengcan Yao
Inflammatory bowel disease (IBD) is a condition of chronic inflammatory intestinal disorder with increasing prevalence but limited effective therapies. The purine metabolic pathway is involved in various inflammatory processes including IBD. However, the mechanisms through which purine metabolism modulates IBD remain to be established. Here we found that mucosal expression of genes involved in the purine metabolic pathway is altered in patients with active ulcerative colitis (UC), which is associated with elevated gene expression signatures of the group 3 innate lymphoid cell (ILC3)-interleukin (IL)-22 pathway...
May 14, 2018: Immunology and Cell Biology
Cindy Audiger, Sylvie Lesage
In contrast to conventional dendritic cells (cDC), when merocytic dendritic cells (mcDC) present antigens derived from apoptotic bodies, T-cell anergy is reversed rather than induced, a process that promotes autoimmunity. Interestingly, mcDC are present in higher proportion in type 1 diabetes-prone NOD mice than in autoimmune-resistant B6 and BALB/c mice, and the Insulin-dependent diabetes (Idd)13 locus is linked to mcDC proportion. Therefore, mcDC are notably associated with susceptibility to autoimmune diabetes...
May 13, 2018: Immunology and Cell Biology
Payam Zarin, Tracy S H In, Edward L Y Chen, Jastaranpreet Singh, Gladys W Wong, Mahmood Mohtashami, David L Wiest, Michele K Anderson, Juan Carlos Zúñiga-Pflücker
γδ T-cells perform a wide range of tissue and disease specific functions that are dependent on the effector cytokines produced by these cells. However, the aggregate signals required for the development of interferon-γ (IFNγ) and interleukin-17 (IL-17) producing γδ T-cells remain unknown. Here, we define the cues involved in the functional programming of γδ T-cells, by examining the roles of T-cell receptor (TCR), Notch, and cytokine-receptor signaling. KN6 γδTCR-transduced Rag2-/- T-cell progenitors were cultured on stromal cells variably expressing TCR and Notch ligands, supplemented with different cytokines...
May 13, 2018: Immunology and Cell Biology
Subhasish Baral, Rahul Roy, Narendra M Dixit
A fraction of chronic hepatitis C patients treated with direct-acting antivirals (DAAs) achieved sustained virological responses (SVR), or cure, despite having detectable viremia at the end of treatment (EOT). This observation, termed EOT+ /SVR, remains puzzling and precludes rational optimization of treatment durations. One hypothesis to explain EOT+ /SVR, the immunologic hypothesis, argues that the viral decline induced by DAAs during treatment reverses the exhaustion of cytotoxic T lymphocytes (CTLs), which then clear the infection after treatment...
May 9, 2018: Immunology and Cell Biology
Morad-Remy Muhsin-Sharafaldine, Alexander Donald McLellan
Although cancer is associated with coagulation disorders, it is still unclear how the combination of tumor cell and host factors enhance the hypercoagulable state of cancer patients. Emerging evidence points to a central role for tumor endosomal and plasma membrane-derived vesicular components in the pathogenesis of cancer-related thrombosis. In particular, tumor cell membranes and extracellular vesicles (EV) harbor lipids and proteinaceous coagulation factors able to initiate multiple points within the coagulation matrix...
May 8, 2018: Immunology and Cell Biology
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