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Cx3cr1

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https://www.readbyqxmd.com/read/28343297/association-of-the-cx3cr1-v249i-variant-with-neurofibrillary-pathology-progression-in-late-onset-alzheimer-s-disease
#1
Alan López-López, Ellen Gelpi, Diana Maria Lopategui, Jose M Vidal-Taboada
Neuroinflammation and microglial dysfunction have a prominent role in the pathogenesis of late-onset Alzheimer's disease (LOAD). CX3CR1 is a microglia-specific gene involved in microglia-neuron crosstalk and neuroinflammation. Numerous evidence show the involvement of CX3CR1 in AD. The aim of this study was to investigate if some functional genetic variants of this gene could influence on LOAD's outcome, in a neuropathologically confirmed Spanish cohort. We designed an open, pragmatic, case-control retrospective study including a total of 475 subjects (205 pathologically confirmed AD cases and 270 controls)...
March 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28342179/common-polymorphisms-of-cx3cr1-gene-modify-als-outcome-a-population-based-study
#2
Andrea Calvo, Cristina Moglia, Antonio Canosa, Stefania Cammarosano, Antonio Ilardi, Davide Bertuzzo, Bryan J Traynor, Maura Brunetti, Marco Barberis, Gabriele Mora, Federico Casale, Adriano Chiò
INTRODUCTION: In the brain the CX3CR1 gene is only expressed by microglia where it acts as a key mediator of the neuron-microglia interactions. We assessed whether the two common polymorphisms of the CX3CR1 gene (V249I and T280M) modify amyotrophic lateral sclerosis (ALS) phenotype. METHODS: The study included 755 ALS patients diagnosed in Piemonte between 2007 and 2012 and 369 age- and gender-matched controls, all genotyped using the same chips. RESULTS: Neither of the variants were associated with an increased risk of ALS...
March 25, 2017: Muscle & Nerve
https://www.readbyqxmd.com/read/28338007/human-immunodeficiency-virus-type-1-myeloid-derived-suppressor-cells-inhibit-cytomegalovirus-inflammation-through-interleukin-27-and-b7-h4
#3
Ankita Garg, Rodney Trout, Stephen A Spector
HIV/CMV co-infected persons despite prolonged viral suppression often experience persistent immune activation, have an increased frequency of myeloid derived suppressor cells (MDSC) and are at increased risk for cardiovascular disease. We examined how HIV MDSC control CD4(+) T cell IFNγ response to a CMVpp65 peptide pool (CMVpp65). We show that HIV/CMV co-infected persons with virologic suppression and recovered CD4(+) T cells compared to HIV(-)/CMV(+) controls exhibit an increase in CD4(+)CX3CR1(+)IFNγ(+) cells in response to CMVpp65; MDSC depletion further augmented CD4(+)CX3CR1(+)IFNγ(+) cells and IFNγ production...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28322863/deep-immune-profiling-by-mass-cytometry-links-human-t-and-nk-cell-differentiation-and-cytotoxic-molecule-expression-patterns
#4
Bertram Bengsch, Takuya Ohtani, Ramin Sedaghat Herati, Niels Bovenschen, Kyong-Mi Chang, E John Wherry
The elimination of infected or tumor cells by direct lysis is a key T and NK cell effector function. T and NK cells can kill target cells by coordinated secretion of cytotoxic granules containing one or both pore-forming proteins, perforin and granulysin and combinations of granzyme (Gzm) family effector proteases (in humans: Gzm A, B, K, M and H). Understanding the pattern of expression of cytotoxic molecules and the relationship to different states of T and NK cells may have direct relevance for immune responses in autoimmunity, infectious disease and cancer...
March 17, 2017: Journal of Immunological Methods
https://www.readbyqxmd.com/read/28320442/analysis-of-monocyte-infiltration-in-mptp-mice-reveals-that-microglial-cx3cr1-protects-against-neurotoxic-over-induction-of-monocyte-attracting-ccl2-by-astrocytes
#5
Vincent R Parillaud, Guillaume Lornet, Yann Monnet, Anne-Laure Privat, Andrei T Haddad, Vanessa Brochard, Amaury Bekaert, Camille Baudesson de Chanville, Etienne C Hirsch, Christophe Combadière, Stéphane Hunot, Christian S Lobsiger
BACKGROUND: Evidence from mice suggests that brain infiltrating immune cells contribute to neurodegeneration, and we previously identified a deleterious lymphocyte infiltration in Parkinson's disease mice. However, this remains controversial for monocytes, due to artifact-prone techniques used to distinguish them from microglia. Our aim was to reassess this open question, by taking advantage of the recent recognition that chemokine receptors CCR2 and CX3CR1 can differentiate between inflammatory monocytes and microglia, enabling to test whether CCR2(+) monocytes infiltrate the brain during dopaminergic (DA) neurodegeneration and whether they contribute to neuronal death...
March 21, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28315475/evolution-of-the-ability-to-modulate-host-chemokine-networks-via-gene-duplication-in-human-cytomegalovirus-hcmv
#6
Jessica A Scarborough, John R Paul, Juliet V Spencer
Human cytomegalovirus (HCMV) is a widespread pathogen that is particularly skillful at evading immune detection and defense mechanisms, largely due to extensive co-evolution with its host. One aspect of this co-evolution involves the acquisition of virally encoded G protein-coupled receptors (GPCRs) with homology to the chemokine receptor family. GPCRs are the largest family of cell surface proteins, found in organisms from yeast to humans, and they regulate a variety of cellular processes including development, sensory perception, and immune cell trafficking...
March 14, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28302649/endothelial-protective-monocyte-patrolling-in-large-arteries-intensified-by-western-diet-and-atherosclerosis
#7
Amado Quintar, Sara McArdle, Dennis Wolf, Alex Marki, Erik Ehinger, Melanie Vassallo, Jacqueline F Miller, Zbigniew Mikulski, Klaus Ley, Konrad Buscher
Rationale: Non-classical mouse monocyte (CX3CR1(high), Ly-6C(low)) patrolling along the vessels of the microcirculation is critical for endothelial homeostasis and inflammation. Due to technical challenges it is currently not established how patrolling occurs in large arteries. Objective: This study was undertaken to elucidate the molecular, migratory and functional phenotype of patrolling monocytes in the high shear and pulsatile environment of large arteries in healthy, hyperlipidemic and atherosclerotic conditions...
March 16, 2017: Circulation Research
https://www.readbyqxmd.com/read/28282403/chemokine-binding-protein-m3-limits-atherosclerosis-in-apolipoprotein-e-mice
#8
Dhanya Ravindran, Anisyah Ridiandries, Laura Z Vanags, Rodney Henriquez, Siân Cartland, Joanne T M Tan, Christina A Bursill
Chemokines are important in macrophage recruitment and the progression of atherosclerosis. The 'M3' chemokine binding protein inactivates key chemokines involved in atherosclerosis (e.g. CCL2, CCL5 and CX3CL1). We aimed to determine the effect of M3 on plaque development and composition. In vitro chemotaxis studies confirmed that M3 protein inhibited the activity of chemokines CCL2, CCL5 and CX3CL1 as primary human monocyte migration as well as CCR2-, CCR5- and CX3CR1-directed migration was attenuated by M3...
2017: PloS One
https://www.readbyqxmd.com/read/28275196/mutating-the-cx3c-motif-in-the-g-protein-should-make-a-live-respiratory-syncytial-virus-vaccine-safer-and-more-effective
#9
S Boyoglu-Barnum, S O Todd, J Meng, T R Barnum, T Chirkova, L M Haynes, S J Jadhao, R A Tripp, A G Oomens, M L Moore, L J Anderson
Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Through a CX3C chemokine motif ((182)CWAIC(186)) in the G protein, RSV binds to the corresponding chemokine receptor, CX3CR1. Since RSV binding to CX3CR1 contributes to disease pathogenesis, we investigated whether a mutation in the CX3C motif by insertion of an alanine A(186) within the CX3C motif to CX4C ((182)CWAIAC(187)), known to block binding to CX3CR1, might decrease disease...
March 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28267793/the-drf-motif-of-cxcr6-as-chemokine-receptor-adaptation-to-adhesion
#10
Andrea Koenen, Aaron Babendreyer, Julian Schumacher, Tobias Pasqualon, Nicole Schwarz, Anke Seifert, Xavier Deupi, Andreas Ludwig, Daniela Dreymueller
The CXC-chemokine receptor 6 (CXCR6) is a class A GTP-binding protein-coupled receptor (GPCRs) that mediates adhesion of leukocytes by interacting with the transmembrane cell surface-expressed chemokine ligand 16 (CXCL16), and also regulates leukocyte migration by interacting with the soluble shed variant of CXCL16. In contrast to virtually all other chemokine receptors with chemotactic activity, CXCR6 carries a DRF motif instead of the typical DRY motif as a key element in receptor activation and G protein coupling...
2017: PloS One
https://www.readbyqxmd.com/read/28264978/deletion-of-the-fractalkine-receptor-cx3cr1-improves-endogenous-repair-axon-sprouting-and-synaptogenesis-after-spinal-cord-injury-in-mice
#11
Camila M Freria, Jodie C E Hall, Ping Wei, Zhen Guan, Dana M McTigue, Phillip G Popovich
Impaired signaling via CX3CR1, the fractalkine receptor, promotes recovery after traumatic spinal contusion injury in mice, a benefit achieved in part by reducing macrophage-mediated injury at the lesion epicenter. Here, we tested the hypothesis that CX3CR1-dependent changes in microglia and macrophage functions also will enhance neuroplasticity, at and several segments below the injury epicenter. New data show that in the presence of inflammatory stimuli, CX3CR1-deficient (CX3CR1(-/-)) microglia and macrophages adopt a reparative phenotype and increase expression of genes that encode neurotrophic and gliogenic proteins...
March 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28264969/cooperation-of-gastric-mononuclear-phagocytes-with-helicobacter-pylori-during-colonization
#12
Monica Viladomiu, Josep Bassaganya-Riera, Nuria Tubau-Juni, Barbara Kronsteiner, Andrew Leber, Casandra W Philipson, Victoria Zoccoli-Rodriguez, Raquel Hontecillas
Helicobacter pylori, the dominant member of the human gastric microbiota, elicits immunoregulatory responses implicated in protective versus pathological outcomes. To evaluate the role of macrophages during infection, we employed a system with a shifted proinflammatory macrophage phenotype by deleting PPARγ in myeloid cells and found a 5- to 10-fold decrease in gastric bacterial loads. Higher levels of colonization in wild-type mice were associated with increased presence of mononuclear phagocytes and in particular with the accumulation of CD11b(+)F4/80(hi)CD64(+)CX3CR1(+) macrophages in the gastric lamina propria...
March 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28264694/cell-specific-deletion-of-c1qa-identifies-microglia-as-the-dominant-source-of-c1q-in-mouse-brain
#13
Maria I Fonseca, Shu-Hui Chu, Michael X Hernandez, Melody J Fang, Lila Modarresi, Pooja Selvan, Grant R MacGregor, Andrea J Tenner
BACKGROUND: The complement cascade not only provides protection from infection but can also mediate destructive inflammation. Complement is also involved in elimination of neuronal synapses which is essential for proper development, but can be detrimental during aging and disease. C1q, required for several of these complement-mediated activities, is present in the neuropil, microglia, and a subset of interneurons in the brain. METHODS: To identify the source(s) of C1q in the brain, the C1qa gene was selectively inactivated in the microglia or Thy-1(+) neurons in both wild type mice and a mouse model of Alzheimer's disease (AD), and C1q synthesis assessed by immunohistochemistry, QPCR, and western blot analysis...
March 6, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28257233/three-unique-interstitial-macrophages-in-the-murine-lung-at-steady-state
#14
Sophie L Gibbings, Stacey M Thomas, Shaikh M Atif, Alexandra L McCubbrey, A Nicole Desch, Thomas Danhorn, Sonia M Leach, Donna L Bratton, Peter M Henson, William J Janssen, Claudia V Jakubzick
RATIONALE: The current paradigm in macrophage biology is that some tissues mainly contain macrophages from embryonic origin such as microglia in the brain, while other tissues contain postnatal-derived macrophages, such as the gut. However, in the lung and in other organs such as the skin, there are both embryonic and postnatal-derived macrophages. OBJECTIVES: In this study, we demonstrate in the steady-state lung that the mononuclear phagocyte system is comprised of three newly identified interstitial macrophages (IMs), alveolar macrophages (AMs), dendritic cells (DCs) and few extravascular monocytes...
March 3, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28256515/activation-of-e-prostanoid-3-receptor-in-macrophages-facilitates-cardiac-healing-after-myocardial-infarction
#15
Juan Tang, Yujun Shen, Guilin Chen, Qiangyou Wan, Kai Wang, Jian Zhang, Jing Qin, Guizhu Liu, Shengkai Zuo, Bo Tao, Yu Yu, Junwen Wang, Michael Lazarus, Ying Yu
Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6C(low) and Ly6C(high)) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E2 is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6C(low) Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones...
March 3, 2017: Nature Communications
https://www.readbyqxmd.com/read/28251165/novel-chemokine-based-immunotoxins-for-potent-and-selective-targeting-of-cytomegalovirus-infected-cells
#16
Katja Spiess, Mads G Jeppesen, Mikkel Malmgaard-Clausen, Karen Krzywkowski, Thomas N Kledal, Mette M Rosenkilde
Immunotoxins as antiviral therapeutics are largely unexplored but have promising prospective due to their high selectivity potential and their unparalleled efficiency. One recent example targeted the virus-encoded G protein-coupled receptor US28 as a strategy for specific and efficient treatment of human cytomegalovirus (HCMV) infections. US28 is expressed on virus-infected cells and scavenge chemokines by rapid internalization. The chemokine-based fusion-toxin protein (FTP) consisted of a variant (F49A) of CX3CL1 specifically targeting US28 linked to the catalytic domain of Pseudomonas exotoxin A (PE)...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28235764/cellular-and-molecular-identity-of-tumor-associated-macrophages-in-glioblastoma
#17
Zhihong Chen, Xi Feng, Cameron J Herting, Virginia Alvarez Garcia, Kai Nie, Winnie W Pong, Rikke Rasmussen, Bhakti Dwivedi, Sandra Seby, Susanne A Wolf, David H Gutmann, Dolores Hambardzumyan
In glioblastoma (GBM), tumor--associated macrophages (TAM) represent up to one half of the cells of the tumor mass, including both infiltrating macrophages and resident brain microglia. In an effort to delineate the temporal and spatial dynamics of TAM composition during gliomagenesis, we employed two genetically engineered mouse models where oncogenic drivers and fluorescent reporters were expressed coordinately under the control of the monocyte/microglia--selective Cx3cr1 or Ccr2 promoters, respectively. Using this approach, we demonstrated that CX3CR1LoCCR2Hi monocytes were recruited to the glioblastoma, where they transitioned to CX3CR1HiCCR2Lo macrophages and CX3CR1HiCCR2- microglia--like cells...
February 24, 2017: Cancer Research
https://www.readbyqxmd.com/read/28234900/role-of-the-cx3c-chemokine-receptor-cx3cr1-in-the-pathogenesis-of-atherosclerosis-after-aortic-transplantation
#18
Zuzanna Rowinska, Thomas A Koeppel, Maryam Sanati, Hubert Schelzig, Joachim Jankowski, Christian Weber, Alma Zernecke, Elisa A Liehn
BACKGROUND: The CX3C chemokine receptor CX3CR1 is expressed on monocytes as well as tissue resident cells, such as smooth muscle cells (SMCs). Its role in atherosclerotic tissue remodeling of the aorta after transplantation has not been investigated. METHODS: We here have orthotopically transplanted infrarenal Cx3cr1-/-Apoe-/- and Cx3cr1+/+Apoe-/- aortic segments into Apoe-/-mice, as well as Apoe-/- aortic segments into Cx3cr1-/-Apoe-/- mice. The intimal plaque size and cellular plaque composition of the transplanted aortic segment were analyzed after four weeks of atherogenic diet...
2017: PloS One
https://www.readbyqxmd.com/read/28228284/respiratory-syncytial-virus-infects-regulatory-b-cells-in-human-neonates-via-chemokine-receptor-cx3cr1-and-promotes-lung-disease-severity
#19
Dania Zhivaki, Sébastien Lemoine, Annick Lim, Ahsen Morva, Pierre-Olivier Vidalain, Liliane Schandene, Nicoletta Casartelli, Marie-Anne Rameix-Welti, Pierre-Louis Hervé, Edith Dériaud, Benoit Beitz, Maryline Ripaux-Lefevre, Jordi Miatello, Brigitte Lemercier, Valerie Lorin, Delphyne Descamps, Jenna Fix, Jean-François Eléouët, Sabine Riffault, Olivier Schwartz, Fabrice Porcheray, Françoise Mascart, Hugo Mouquet, Xiaoming Zhang, Pierre Tissières, Richard Lo-Man
Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infections in infants and is characterized by pulmonary infiltration of B cells in fatal cases. We analyzed the B cell compartment in human newborns and identified a population of neonatal regulatory B lymphocytes (nBreg cells) that produced interleukin 10 (IL-10) in response to RSV infection. The polyreactive B cell receptor of nBreg cells interacted with RSV protein F and induced upregulation of chemokine receptor CX3CR1. CX3CR1 interacted with RSV glycoprotein G, leading to nBreg cell infection and IL-10 production that dampened T helper 1 (Th1) cytokine production...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28223698/sex-differences-in-microglial-cx3cr1-signalling-determine-obesity-susceptibility-in-mice
#20
Mauricio D Dorfman, Jordan E Krull, John D Douglass, Rachael Fasnacht, Fernando Lara-Lince, Thomas H Meek, Xiaogang Shi, Vincent Damian, Hong T Nguyen, Miles E Matsen, Gregory J Morton, Joshua P Thaler
Female mice are less susceptible to the negative metabolic consequences of high-fat diet feeding than male mice, for reasons that are incompletely understood. Here we identify sex-specific differences in hypothalamic microglial activation via the CX3CL1-CX3CR1 pathway that mediate the resistance of female mice to diet-induced obesity. Female mice fed a high-fat diet maintain CX3CL1-CX3CR1 levels while male mice show reductions in both ligand and receptor expression. Female Cx3cr1 knockout mice develop 'male-like' hypothalamic microglial accumulation and activation, accompanied by a marked increase in their susceptibility to diet-induced obesity...
February 22, 2017: Nature Communications
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