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https://www.readbyqxmd.com/read/28088061/galectins-emerging-regulatory-checkpoints-linking-tumor-immunity-and-angiogenesis
#1
REVIEW
Santiago P Méndez-Huergo, Ada G Blidner, Gabriel A Rabinovich
Immune checkpoints, a plethora of inhibitory pathways aimed at maintaining immune cell homeostasis, may be co-opted by cancer cells to evade immune destruction. Therapies targeting immune checkpoints have reached a momentum yielding significant clinical benefits in patients with various malignancies by unleashing anti-tumor immunity. Galectins, a family of glycan-binding proteins, have emerged as novel regulatory checkpoints that promote immune evasive programs by inducing T-cell exhaustion, limiting T-cell survival, favoring expansion of regulatory T cells, de-activating natural killer cells and polarizing myeloid cells toward an immunosuppressive phenotype...
January 11, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28087948/regulation-of-immunity-to-tuberculosis
#2
Susanna Brighenti, Diane J Ordway
Immunity against Mycobacterium tuberculosis requires a balance between adaptive immune responses to constrain bacterial replication and the prevention of potentially damaging immune activation. Regulatory T (Treg) cells express the transcription factor Foxp3+ and constitute an essential counterbalance of inflammatory Th1 responses and are required to maintain immune homeostasis. The first reports describing the presence of Foxp3-expressing CD4+ Treg cells in tuberculosis (TB) emerged in 2006. Different Treg cell subsets, most likely specialized for different tissues and microenvironments, have been shown to expand in both human TB and animal models of TB...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087945/innate-immune-responses-to-tuberculosis
#3
Jeffrey S Schorey, Larry S Schlesinger
Tuberculosis remains one of the greatest threats to human health. The causative bacterium, Mycobacterium tuberculosis, is acquired by the respiratory route. It is exquisitely adapted to humans and is a prototypic intracellular pathogen of macrophages, with alveolar macrophages being the primary conduit of infection and disease. However, M. tuberculosis bacilli interact with and are affected by several soluble and cellular components of the innate immune system which dictate the outcome of primary infection, most commonly a latently infected healthy human host, in whom the bacteria are held in check by the host immune response within the confines of tissue granuloma, the host histopathologic hallmark...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087941/interplay-between-myeloid-cells-and-humoral-innate-immunity
#4
Sébastien Jaillon, Eduardo Bonavita, Cecilia Garlanda, Alberto Mantovani
The innate immune system represents the first line of defense against pathogens and comprises both a cellular and a humoral arm. Fluid-phase pattern recognition molecules (PRMs), which include collectins, ficolins, and pentraxins, are key components of the humoral arm of innate immunity and are expressed by a variety of cells, including myeloid, epithelial, and endothelial cells, mainly in response to infectious and inflammatory conditions. Soluble PRMs share basic multifunctional properties including activation and regulation of the complement cascade, opsonization of pathogens and apoptotic cells, regulation of leukocyte extravasation, and fine-tuning of inflammation...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087940/the-memory-immune-response-to-tuberculosis
#5
Joanna R Kirman, Marcela I Henao-Tamayo, Else Marie Agger
Immunological memory is a central feature of the adaptive immune system and a prerequisite for generating effective vaccines. Understanding long-term memory responses to Mycobacterium tuberculosis will thus provide us with valuable insights that can guide us in the search for a novel vaccine against tuberculosis (TB). For many years, triggering CD4 T cells and, in particular, those secreting interferon-γ has been the goal of most TB vaccine research, and numerous data from animals and humans support the key role of this subset in protective immunity...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087939/dendritic-cells-in-the-immune-system-history-lineages-tissues-tolerance-and-immunity
#6
Jonathan M Austyn
The aim of this review is to provide a coherent framework for understanding dendritic cells (DCs). It has seven sections. The introduction provides an overview of the immune system and essential concepts, particularly for the nonspecialist reader. Next, the "History" section outlines the early evolution of ideas about DCs and highlights some sources of confusion that still exist today. The "Lineages" section then focuses on five different populations of DCs: two subsets of "classical" DCs, plasmacytoid DCs, monocyte-derived DCs, and Langerhans cells...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087938/the-role-and-function-of-fc%C3%AE-receptors-on-myeloid-cells
#7
Stylianos Bournazos, Taia T Wang, Jeffrey V Ravetch
A key determinant for the survival of organisms is their capacity to recognize and respond efficiently to foreign antigens. This is largely accomplished by the orchestrated activity of the innate and adaptive branches of the immune system. Antibodies are specifically generated in response to foreign antigens, facilitating thereby the specific recognition of antigens of almost infinite diversity. Receptors specific for the Fc domain of antibodies, Fc receptors, are expressed on the surface of the various myeloid leukocyte populations and mediate the binding and recognition of antibodies by innate leukocytes...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087937/myeloid-cell-phenotypes-in-susceptibility-and-resistance-to-helminth-parasite-infections
#8
Rick M Maizels, James P Hewitson
Many major tropical diseases are caused by long-lived helminth parasites that are able to survive by modulation of the host immune system, including the innate compartment of myeloid cells. In particular, dendritic cells and macrophages show markedly altered phenotypes during parasite infections. In addition, many specialized subsets such as eosinophils and basophils expand dramatically in response to these pathogens. The changes in phenotype and function, and their effects on both immunity to infection and reactivity to bystander antigens such as allergens, are discussed...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087931/evolution-of-cell-autonomous-effector-mechanisms-in-macrophages-versus-non-immune-cells
#9
Ryan G Gaudet, Clinton J Bradfield, John D MacMicking
Specialized adaptations for killing microbes are synonymous with phagocytic cells including macrophages, monocytes, inflammatory neutrophils, and eosinophils. Recent genome sequencing of extant species, however, reveals that analogous antimicrobial machineries exist in certain non-immune cells and also within species that ostensibly lack a well-defined immune system. Here we probe the evolutionary record for clues about the ancient and diverse phylogenetic origins of macrophage killing mechanisms and how some of their properties are shared with cells outside the traditional bounds of immunity in higher vertebrates such as mammals...
December 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087924/clinical-testing-of-tuberculosis-vaccine-candidates
#10
Mark Hatherill, Dereck Tait, Helen McShane
It is almost 100 years since the development of bacille Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis (TB). While BCG does confer consistent protection against disseminated disease, there is an urgent need for a more effective vaccine against pulmonary disease. There are several indications for such an improved vaccine, including prevention of infection, prevention of disease, and a therapeutic vaccine to prevent recurrent disease. The two main approaches to TB vaccine development are developing an improved whole mycobacterial priming agent to replace BCG and/or developing a subunit booster vaccine to be administered after a BCG or BCG replacement priming vaccination...
October 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28087918/-research-progress-on-the-role-of-tank-binding-kinase-1-in-anti-virus-innate-immune-response
#11
Xue Wang, Yuchuan Zhang, Wei Chen
The innate immune response against viral infection is mainly relies on type I interferon, the production of which is mediated by TANK-binding kinase 1 (TBK1). It is revealed that the downstream TBK1 is activated by viral nucleic acid sensors RIG-I, cGAS and TLR3. The activity of TBK1 is complexly and precisely regulated by different type of protein modifications, including phosphorylation, ubiquitination and Sumolylation. This article focuses on the role of TBK1 in anti-viral innate immunity and the regulatory mechanism for the TBK1 activation...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087912/-t-cell-receptor-%C3%AE-chain-cdr3-spectratyping-and-cytomegalovirus-activation-in-allogeneic-hematopoietic-stem-cell-transplant-recipients
#12
Zhihua Wu, Min Jing, Hanying Liang, Rong Yang, Yaping Huang, Xiaoming Chen, Jianhua Hu, Jun Fan
Objective: To explore the association between T-cell receptor beta variable (TCR BV) complementarity determining region 3 (CDR3) spectratyping and CMV activation in the recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Methods: Fluorescence quantitative PCR melting curve analysis was used to sequence 24 TCR BV families in 7 HSCT recipients and 3 healthy controls. CMV-pp65 antigenemia was measured by immunohistochemical staining. Plasma IgM specific for CMV was identified using ELISA. Relationship between TCR BV families and CMV activation was statistically analyzed...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087881/role-of-stim2-in-cell-function-and-physiopathology
#13
Alejandro Berna-Erro, Isaac Jardin, Gines M Salido, Juan A Rosado
An endoplasmic reticulum (ER)-resident protein that regulates cytosolic and ER free-Ca(2+) concentration by induction of store-operated calcium entry. That is the original definition of STIM2 and its function. While its activity strongly depends on the amount of calcium stored in the ER, its function goes further to intracellular signalling and gene expression. Initially undercovered by the prominent function of STIM1, STIM2 became to be vital in mice, gradually emerging as an important player in the nervous system, and cooperating with STIM1 in the immune system...
January 14, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28087841/single-cell-transcriptome-analysis-of-fish-immune-cells-provides-insight-into-the-evolution-of-vertebrate-immune-cell-types
#14
Santiago J Carmona, Sarah A Teichmann, Lauren Ferreira, Iain C Macaulay, Michael J T Stubbington, Ana Cvejic, David Gfeller
The immune system of vertebrate species consists of many different cell types that have distinct functional roles and are subject to different evolutionary pressures. Here, we first analysed conservation of genes specific for all major immune cell types in human and mouse. Our results revealed higher gene turnover and faster evolution of trans-membrane proteins in NK cells compared to other immune cell types, and especially T cells, but similar conservation of nuclear and cytoplasmic protein coding genes. To validate these findings in a distant vertebrate species, we used single-cell RNA-Sequencing of lck:GFP cells in zebrafish and obtained the first transcriptome of specific immune cell types in a non-mammalian species...
January 13, 2017: Genome Research
https://www.readbyqxmd.com/read/28087830/recognition-of-the-magnaporthe-oryzae-effector-avr-pia-by-the-decoy-domain-of-the-rice-nlr-immune-receptor-rga5
#15
Diana Ortiz, Karine De Guillen, Stella Cesari, Véronique Chalvon, Jérome Gracy, André Padilla, Thomas Kroj
Nucleotide-binding domain and leucine-rich repeat proteins (NLRs) are important receptors in plant immunity that allow recognition of pathogen effectors. The rice NLR RGA5 recognizes the Magnaporthe oryzae effector AVR-Pia through direct interaction. Here, we gained detailed insights into the molecular and structural bases of AVR-Pia-RGA5 interaction and the role of the RATX1 decoy domain of RGA5. NMR titration combined with in vitro and in vivo protein-protein interaction analyses identified the AVR-Pia interaction surface that binds to the RATX1 domain...
January 13, 2017: Plant Cell
https://www.readbyqxmd.com/read/28087809/trim13-potentiates-tlr2-mediated-nf-%C3%AE%C2%BAb-activation-via-k29-linked-polyubiquitination-of-traf6
#16
Bin Huang, Suk-Hwan Baek
Ubiquitination is a versatile post-translational modification involved in NF-κB activation of TLR signaling. Here, we demonstrated that Trim13, an E3 ubiquitin ligase, is up-regulated in macrophages upon stimulation with TLR2 ligand. Knock-down of Trim13 attenuated TLR2-mediated production of cytokines/chemokines and formation of foam cells, as well as activation of NF-κB. Trim13 interacts with TRAF6 and potentiates NF-κB activity via ubiquitination of TRAF6. Overexpression of inactive mutant (C10/13A) or RING deletion mutant of Trim13 did not potentiate ubiquitination of TRAF6 or activation of NF-κB...
January 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28087806/splenectomy-does-not-improve-long-term-outcome-after-stroke
#17
Dannielle Zierath, Angela Shen, Astiana Stults, Theresa Olmstead, Kyra J Becker
BACKGROUND AND PURPOSE: Immune responses to brain antigens after stroke contribute to poor outcome. We hypothesized that splenectomy would lessen the development of such responses and improve outcome. METHODS: Male Lewis rats (275-350 g) underwent 2-hour middle cerebral artery occlusion immediately after splenectomy or sham splenectomy. Animals were survived to 4 weeks (672 hrs), and immune responses to myelin basic protein determined at euthanasia. Infarct volume was determined in a subset of animals euthanized at 72 hours...
January 13, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28087775/rapid-expansion-of-immune-related-gene-families-in-the-house-fly-musca-domestica
#18
Timothy B Sackton, Brian P Lazzaro, Clark G Andrew
The house fly, Musca domestica, occupies an unusual diversity of potentially septic niches compared to other sequenced Dipteran insects and is a vector of numerous diseases of humans and livestock. In the present study, we apply whole-transcriptome sequencing to identify genes whose expression is regulated in adult flies upon bacterial infection. We then combine the transcriptomic data with analysis of rates of gene duplication and loss to provide insight into the evolutionary dynamics of immune-related genes...
January 12, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28087772/possible-roles-of-new-mutations-shared-by-asian-and-american-zika-viruses
#19
Shozo Yokoyama, William T Starmer
Originating in Africa, the Zika virus (ZIKV) has spread to Asia, Pacific Islands and now to the Americas and beyond. Since the first isolation in 1947, ZIKV strains have been sampled at various times in the last 69 years, but this history has not been reflected in studying the patterns of mutation accumulation in their genomes. Implementing the viral history, we show that the ZIKV ancestor appeared sometime in 1930-1945 and, at that point, its mutation rate was probably less than 0.2 x 10(-3)/nucleotide site/year and subsequently increased significantly in most of its descendants...
January 12, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28087676/the-longitudinal-study-of-aging-in-human-young-adults-knowledge-gaps-and-research-agenda
#20
Terrie E Moffitt, Daniel W Belsky, Andrea Danese, Richie Poulton, Avshalom Caspi
BACKGROUND: To prevent onset of age-related diseases and physical and cognitive decline, interventions to slow human aging and extend health span must eventually be applied to people while they are still young and healthy. Yet most human aging research examines older adults, many with chronic disease, and little is known about aging in healthy young humans. METHOD: This article explains how this knowledge gap is a barrier to extending health span and puts forward the case that geroscience should invest in researching the pace of aging in young adults...
February 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
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