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https://www.readbyqxmd.com/read/29317703/modeling-tumor-immunity-of-mouse-glioblastoma-by-exhausted-cd8-t-cells
#1
Hiroshi Nakashima, Quazim A Alayo, Pablo Penaloza-MacMaster, Gordon J Freeman, Vijay K Kuchroo, David A Reardon, Soledad Fernandez, Michael Caligiuri, E Antonio Chiocca
T cell exhaustion occurs during chronic infection and cancers. Programmed cell death protein-1 (PD-1) is a major inhibitory checkpoint receptor involved in T cell exhaustion. Blocking antibodies (Abs) against PD-1 or its ligand, PD-L1, have been shown to reverse T cell exhaustion during chronic infection and cancers, leading to improved control of persistent antigen. However, modeling tumor-specific T cell responses in mouse has been difficult due to the lack of reagents to detect and phenotype tumor-specific immune responses...
January 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29315553/acute-stimulation-generates-tim-3-expressing-th1-type-cd4-t-cells-that-persist-in-vivo-and-show-enhanced-effector-function
#2
Jacob V Gorman, John D Colgan
Tim-3 is a surface receptor expressed by Th1-type effector CD4 T cells, which are critical for defense against intracellular pathogens and have been implicated in autoimmune disease. Previous studies showed Tim-3 expression makes Th1 cells more susceptible to apoptosis and also marks functionally impaired T cells that arise due to chronic stimulation. However, other studies suggested Tim-3-expressing Th1 cells do not always have these properties. To further define the relationship between Tim-3 and Th1 cell function, we analyzed the characteristics of Th1 cells that expressed Tim-3 in response to brief stimulation in vitro or an acute viral infection in vivo...
January 9, 2018: Immunology
https://www.readbyqxmd.com/read/29311359/the-effects-of-dendritic-cell-hypersensitivity-on-persistent-viral-infection
#3
Jennifer S Tsau, Xin Huang, Chen-Yen Lai, Stephen M Hedrick
Caspase-8 (CASP8) is known as an executioner of apoptosis, but more recent studies have shown that it participates in the regulation of necroptosis and innate immunity. In this study, we show that CASP8 negatively regulates retinoic acid-inducible gene I (RIG-I) signaling such that, in its absence, stimulation of the RIG-I pathway in dendritic cells (DCs) produced modestly enhanced activation of IFN regulatory factor 3 with correspondingly greater amounts of proinflammatory cytokines. In addition, mice lacking DC-specific CASP8 (dcCasp8-/- mice) develop age-dependent symptoms of autoimmune disease characterized by hyperactive DCs and T cells, spleen and liver immunopathology, and the appearance of Th1-polarized CD4+ T cells...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29301196/sustained-ifn-i-expression-during-established-persistent-viral-infection-a-bad-seed-for-protective-immunity
#4
REVIEW
Xavier Dagenais-Lussier, Hamza Loucif, Armstrong Murira, Xavier Laulhé, Simona Stäger, Alain Lamarre, Julien van Grevenynghe
Type I interferons (IFN-I) are one of the primary immune defenses against viruses. Similar to all other molecular mechanisms that are central to eliciting protective immune responses, IFN-I expression is subject to homeostatic controls that regulate cytokine levels upon clearing the infection. However, in the case of established persistent viral infection, sustained elevation of IFN-I expression bears deleterious effects to the host and is today considered as the major driver of inflammation and immunosuppression...
December 30, 2017: Viruses
https://www.readbyqxmd.com/read/29296930/gene-transfer-into-hematopoietic-stem-cells-reduces-hlh-manifestations-in-a-murine-model-of-munc13-4-deficiency
#5
Tayebeh Soheili, Amandine Durand, Fernando E Sepulveda, Julie Rivière, Chantal Lagresle-Peyrou, Hanem Sadek, Geneviève de Saint Basile, Samia Martin, Fulvio Mavilio, Marina Cavazzana, Isabelle André-Schmutz
Patients with mutations in the UNC13D gene (coding for Munc13-4 protein) suffer from familial hemophagocytic lymphohistiocytosis type 3 (FHL3), a life-threatening immune and hyperinflammatory disorder. The only curative treatment is allogeneic hematopoietic stem cell (HSC) transplantation, although the posttreatment survival rate is not satisfactory. Here, we demonstrate the curative potential of UNC13D gene correction of HSCs in a murine model of FHL3. We generated a self-inactivating lentiviral vector, used it to complement HSCs from Unc13d-deficient (Jinx) mice, and transplanted the cells back into the irradiated Jinx recipients...
December 26, 2017: Blood Advances
https://www.readbyqxmd.com/read/29278020/diagnosis-and-management-of-lyme-neuroborreliosis
#6
John J Halperin
The nervous system is involved in 10-15% of patients infected with B. burgdorferi, B. afzelii and B. garinii. This review will address widespread misconceptions about the clinical phenomenology, diagnostic approach and response to treatment of neuroborreliosis. Areas covered: Improvements in diagnostic testing have allowed better definition of the clinical spectrum of neuroborreliosis, with lymphocytic meningitis and uni- or multifocal inflammation of peripheral/cranial nerves predominating. Despite widespread concern that post-treatment cognitive/behavioral symptoms might be attributable to persisting infection or aberrant inflammation within the central nervous system a large body of evidence indicates this is extremely improbable...
January 2018: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/29276185/non-viable-lactobacillus-casei-beneficially-modulates-poly-i-c-immune-response-in-co-cultures-of-human-cells
#7
Elisa Vintiñi, Marcela Medina
BACKGROUND: Polyinosinic:polycytidylic acid (Poly-IC) has been used as a viral stimulus to mimic in vivo and in vitro infection induced by some viruses. OBJECTIVE: To determine whether non-viable Lactobacillus casei CRL431 (LcM) can modulate the immune response induced by Poly I:C in co-culture models of peripheral blood mononuclear cells (PBMC) and A549 cells. METHODS: T and NK cell activation was evaluated by flow cytometry and levels of TNF-α, IFN-γ, IL-10, IL-29, and IL-17 by ELISA...
December 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/29274774/nanotherapy-for-alzheimer-s-disease-and-vascular-dementia-targeting-senile-endothelium
#8
REVIEW
Joseph S D'Arrigo
Due to the complexity of Alzheimer's disease, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted lipid nanoemulsion) are available. Versatile small molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted "lipid-coated microbubble" [LCM]/"nanoparticle-derived" [ND] (or LCM/ND) nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine...
December 8, 2017: Advances in Colloid and Interface Science
https://www.readbyqxmd.com/read/29274373/congenital-lymphocytic-choriomeningitis-virus-an-underdiagnosed-fetal-teratogen
#9
Michael Kinori, Hal Schwartzstein, Janice Lasky Zeid, Sudhi P Kurup, Marilyn B Mets
No abstract text is available yet for this article.
December 20, 2017: Journal of AAPOS: the Official Publication of the American Association for Pediatric Ophthalmology and Strabismus
https://www.readbyqxmd.com/read/29261807/characterization-of-host-proteins-interacting-with-the-lymphocytic-choriomeningitis-virus-l-protein
#10
Kseniya Khamina, Alexander Lercher, Michael Caldera, Christopher Schliehe, Bojan Vilagos, Mehmet Sahin, Lindsay Kosack, Anannya Bhattacharya, Peter Májek, Alexey Stukalov, Roberto Sacco, Leo C James, Daniel D Pinschewer, Keiryn L Bennett, Jörg Menche, Andreas Bergthaler
RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics...
December 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29250063/m-il-4-tissue-macrophages-support-efficient-interferon-gamma-production-in-antigen-specific-cd8-t-cells-with-reduced-proliferative-capacity
#11
Rylend Mulder, Andra Banete, Kyle Seaver, Sameh Basta
CD8+ cytotoxic T cell (CTL) responses are necessary for the lysis of virally infected cells and control of infection. CTLs are activated when their TCRs bind a major histocompatibility complex (MHC)-I/peptide complex on the surface of antigen presenting cells such as macrophages (MΦ). It is now apparent that MΦ display remarkable plasticity in response to environmental signals to polarize into classically activated M(LPS + IFN-γ) or alternatively activated M(IL-4). However, little is known about how MΦ activation status influences their antigen presentation function to CD8+ T cell in models of virus infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29246443/transcription-factor-irf4-promotes-cd8-t-cell-exhaustion-and-limits-the-development-of-memory-like-t-cells-during-chronic-infection
#12
Kevin Man, Sarah S Gabriel, Yang Liao, Renee Gloury, Simon Preston, Darren C Henstridge, Marc Pellegrini, Dietmar Zehn, Friederike Berberich-Siebelt, Mark A Febbraio, Wei Shi, Axel Kallies
During chronic stimulation, CD8+ T cells acquire an exhausted phenotype characterized by expression of inhibitory receptors, down-modulation of effector function, and metabolic impairments. T cell exhaustion protects from excessive immunopathology but limits clearance of virus-infected or tumor cells. We transcriptionally profiled antigen-specific T cells from mice infected lymphocytic choriomeningitis virus strains that cause acute or chronic disease. T cell exhaustion during chronic infection was driven by high amounts of T cell receptor (TCR)-induced transcription factors IRF4, BATF, and NFATc1...
December 11, 2017: Immunity
https://www.readbyqxmd.com/read/29237830/axl-can-serve-as-entry-factor-for-lassa-virus-depending-on-the-functional-glycosylation-of-dystroglycan
#13
Chiara Fedeli, Giulia Torriani, Clara Galan-Navarro, Marie-Laurence Moraz, Hector Moreno, Gisa Gerold, Stefan Kunz
Fatal infection with the highly pathogenic Lassa virus (LASV) is characterized by extensive viral dissemination, indicating broad tissue tropism. The major cellular receptor for LASV is the highly conserved extracellular matrix receptor dystroglycan (DG). Binding of LASV depends on DG's tissue-specific post-translational modification with the unusual O-linked polysaccharide matriglycan. Interestingly, functional glycosylation of DG does not always correlate with viral tropism observed in vivo The broadly expressed phosphatidylserine (PS) receptors Axl and Tyro3 were recently identified as alternative LASV receptor candidates...
December 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29236683/effector-cd8-t-cells-dedifferentiate-into-long-lived-memory-cells
#14
Ben Youngblood, J Scott Hale, Haydn T Kissick, Eunseon Ahn, Xiaojin Xu, Andreas Wieland, Koichi Araki, Erin E West, Hazem E Ghoneim, Yiping Fan, Pranay Dogra, Carl W Davis, Bogumila T Konieczny, Rustom Antia, Xiaodong Cheng, Rafi Ahmed
Memory CD8 T cells that circulate in the blood and are present in lymphoid organs are an essential component of long-lived T cell immunity. These memory CD8 T cells remain poised to rapidly elaborate effector functions upon re-exposure to pathogens, but also have many properties in common with naive cells, including pluripotency and the ability to migrate to the lymph nodes and spleen. Thus, memory cells embody features of both naive and effector cells, fuelling a long-standing debate centred on whether memory T cells develop from effector cells or directly from naive cells...
December 13, 2017: Nature
https://www.readbyqxmd.com/read/29223998/cryptococcal-meningitis-in-apparently-immunocompetent-patients-association-with-idiopathic-cd4-lymphopenia
#15
Samuel Shribman, Alastair Noyce, Sharmilee Gnanapavan, Jonathan Lambourne, Thomas Harrison, Frederick Schon
We present two cases of cryptococcal meningitis in people subsequently diagnosed with idiopathic CD4+ lymphopenia. Both presented with new onset headaches without sinister features and were sent home on multiple occasions from emergency departments. Cryptococcal meningitis in HIV-negative patients poses major diagnostic and management problems; the associated mortality is 9%-27%. We suggest performing blood and cerebrospinal fluid cryptococcal antigen tests in all people with lymphocytic meningitis.
December 9, 2017: Practical Neurology
https://www.readbyqxmd.com/read/29222172/proximal-aberrant-crypt-foci-associate-with-synchronous-neoplasia-and-are-primed-for-neoplastic-progression
#16
David A Drew, Allen Mo, James J Grady, Richard G Stevens, Joel B Levine, Bruce M Brenner, Joseph C Anderson, Faripour Forouhar, Michael J O'Brien, Thomas J Devers, Daniel W Rosenberg
Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion found within the human colon. Despite their relatively high frequency in the distal colon, few studies have examined the molecular characteristics of ACF within the proximal colon. In the following study, clinical participants (n=184) were screened for ACF using high-definition chromoendoscopy with contrast dye-spray. Following pathological confirmation, ACF biopsies were subjected to laser-capture microdissection (LCM) and epithelial cells were evaluated for somatic mutations with a customized colorectal cancer mutation panel using DNA-mass spectrometry...
December 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29222166/effect-of-il-7-therapy-on-phospho-ribosomal-protein-s6-and-traf1-expression-in-hiv-specific-cd8-t-cells-in-patients-receiving-antiretroviral-therapy
#17
Chao Wang, Maria I Edilova, Lisa E Wagar, Shariq Mujib, Meromit Singer, Nicole F Bernard, Thérèse Croughs, Michael M Lederman, Irini Sereti, Margaret A Fischl, Elisabeth Kremmer, Mario Ostrowski, Jean-Pierre Routy, Tania H Watts
IL-7 therapy has been evaluated in patients who do not regain normal CD4 T cell counts after virologically successful antiretroviral therapy. IL-7 increases total circulating CD4 and CD8 T cell counts; however, its effect on HIV-specific CD8 T cells has not been fully examined. TRAF1, a prosurvival signaling adaptor required for 4-1BB-mediated costimulation, is lost from chronically stimulated virus-specific CD8 T cells with progression of HIV infection in humans and during chronic lymphocytic choriomeningitis infection in mice...
December 8, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29213267/revealing-the-complexity-in-cd8-t-cell-responses-to-infection-in-inbred-c57b-6-versus-outbred-swiss-mice
#18
Matthew D Martin, Derek B Danahy, Stacey M Hartwig, John T Harty, Vladimir P Badovinac
Recent work has suggested that current mouse models may underrepresent the complexity of human immune responses. While most mouse immunology studies utilize inbred mouse strains, it is unclear if conclusions drawn from inbred mice can be extended to all mouse strains or generalized to humans. We recently described a "surrogate activation marker" approach that could be used to track polyclonal CD8 T cell responses in inbred and outbred mice and noted substantial discord in the magnitude and kinetics of CD8 T cell responses in individual outbred mice following infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29212906/osteoblasts-are-rapidly-ablated-by-virus-induced-systemic-inflammation-following-lymphocytic-choriomeningitis-virus-or-pneumonia-virus-of-mice-infection-in-mice
#19
Steven Maltby, Alyssa J Lochrin, Bianca Bartlett, Hock L Tay, Jessica Weaver, Ingrid J Poulton, Maximilian W Plank, Helene F Rosenberg, Natalie A Sims, Paul S Foster
A link between inflammatory disease and bone loss is now recognized. However, limited data exist on the impact of virus infection on bone loss and regeneration. Bone loss results from an imbalance in remodeling, the physiological process whereby the skeleton undergoes continual cycles of formation and resorption. The specific molecular and cellular mechanisms linking virus-induced inflammation to bone loss remain unclear. In the current study, we provide evidence that infection of mice with either lymphocytic choriomeningitis virus (LCMV) or pneumonia virus of mice (PVM) resulted in rapid and substantial loss of osteoblasts from the bone surface...
December 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29206212/quartz-crystal-microbalance-electronic-interfacing-systems-a-review
#20
REVIEW
Abdulrahman Alassi, Mohieddine Benammar, Dan Brett
Quartz Crystal Microbalance (QCM) sensors are actively being implemented in various fields due to their compatibility with different operating conditions in gaseous/liquid mediums for a wide range of measurements. This trend has been matched by the parallel advancement in tailored electronic interfacing systems for QCM sensors. That is, selecting the appropriate electronic circuit is vital for accurate sensor measurements. Many techniques were developed over time to cover the expanding measurement requirements (e...
December 5, 2017: Sensors
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