DOCSLIB.ORG

Gene Expression Polarization

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Gene Expression Polarization Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression This information is current as of September 27, 2021. Fernando O. Martinez, Siamon Gordon, Massimo Locati and Alberto Mantovani J Immunol 2006; 177:7303-7311; ; doi: 10.4049/jimmunol.177.10.7303 http://www.jimmunol.org/content/177/10/7303 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2006/11/03/177.10.7303.DC1 Material http://www.jimmunol.org/ References This article cites 61 articles, 22 of which you can access for free at: http://www.jimmunol.org/content/177/10/7303.full#ref-list-1 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision by guest on September 27, 2021 • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2006 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Transcriptional Profiling of the Human Monocyte-to-Macrophage Differentiation and Polarization: New Molecules and Patterns of Gene Expression1 Fernando O. Martinez,*† Siamon Gordon,‡ Massimo Locati,2*† and Alberto Mantovani*† Comprehensive analysis of the gene expression profiles associated with human monocyte-to-macrophage differentiation and polarization toward M1 or M2 phenotypes led to the following main results: 1) M-CSF-driven monocyte-to-macrophage differentiation is associated with activation of cell cycle genes, substantiating the underestimated proliferation potential of monocytes. 2) M-CSF leads to expression of a substantial part of the M2 transcriptome, suggesting that under homeostatic conditions a default shift toward M2 occurs. 3) Modulation of genes involved in metabolic activities is a prominent feature of macrophage differentiation and polarization. 4) Lipid metabolism is a main category of modulated transcripts, with Downloaded from expected up-regulation of cyclo-oxygenase 2 in M1 cells and unexpected cyclo-oxygenase 1 up-regulation in M2 cells. 5) Each step is characterized by a different repertoire of G protein-coupled receptors, with five nucleotide receptors as novel M2- associated genes. 6) The chemokinome of polarized macrophages is profoundly diverse and new differentially expressed chemokines are reported. Thus, transcriptome profiling reveals novel molecules and signatures associated with human monocyte-to-macrophage differentiation and polarized activation which may represent candidate targets in pathophysiology. The Journal of Immunology, 2006, 177: 7303–7311. http://www.jimmunol.org/ onocytes and tissue macrophages provide both imme- ygen and nitrogen intermediates) and inflammatory cytokines (IL- diate defense against foreign agents and assist during 1␤, TNF, IL-6), contribute as inducer and effector cells in the setting off and development of the adaptive im- polarized Th1 responses, and mediate resistance against intracel- M ϩ mune response. Monocytes originally derive from CD34 myeloid lular parasites and tumors (7–11). In contrast, the alternative M2 progenitor cells in the bone marrow, circulate in the bloodstream, form of macrophage activation is a generic name used for various and enter peripheral tissues where they mature into different types forms of nonclassically activated macrophages resulting from cell of resident macrophages, characterized by low oxygen consump- exposure to IL-4 or IL-13, immune complexes, IL-10, glucocorti- tion, low protein synthesis rate, and modest cytokine production coid, or secosteroid (vitamin D3) hormones (3, 9, 12). The various by guest on September 27, 2021 (1, 2). Inflammation due to tissue damage or infection results in forms of M2 macrophages share an IL-12low and IL-23low pheno- resident macrophage activation, which increases the production of type, generally display high levels of scavenger, mannose (13), and cytokines, chemokines, and other inflammatory mediators, as well galactose-type receptors (3), and arginine metabolism is shifted to as monocyte recruitment. In the context of specific immune re- production of ornithine and polyamines via arginase (14). sponse, the cytokine milieu compels mononuclear phagocytes to Previous studies have addressed the issue of profiling gene ex- express specialized and polarized functional properties. Mirroring pression in M1 or M2 macrophage activation in the mouse, leading the Th1/Th2 nomenclature, many refer to polarized macrophages to the identification of new molecules expressed in polarized mu- as M1 and M2 cells (3–6). Classically polarized activated M1 rine macrophages (e.g., Ym1, Fizz1, MRC1) (13, 15, 16). Data on macrophages have long been known to be induced by IFN-␥ alone human mononuclear phagocytes on the contrary are scanty and or in concert with microbial stimuli as LPS, or cytokines as TNF have highlighted important interspecies differences in key mole- and GM-CSF. M1 cells have an IL-12high, IL-23high, IL-10low phe- cules, such as arginase and inducible NO synthase, rendering dif- notype, are proficient producers of effector molecules (reactive ox- ficult extrapolation (17, 18). In this study, we report for the first time a whole genome transcriptional profile analysis of the human monocyte-to-macrophage differentiation and polarized activation *Istituto Clinico Humanitas, Rozzano, Italy; †Institute of General Pathology, Univer- sity of Milan, Milan, Italy; and ‡Sir William Dunn School of Pathology, University processes, describing distinct molecular signatures which shed of Oxford, Oxford, United Kingdom new light on these processes and reveal new candidate markers. Received for publication March 9, 2006. Accepted for publication August 3, 2006. The costs of publication of this article were defrayed in part by the payment of page Materials and Methods charges. This article must therefore be hereby marked advertisement in accordance Reagents with 18 U.S.C. Section 1734 solely to indicate this fact. 1 This work was supported by the Italian Association for Cancer Research, Ministero Recombinant human cytokines were obtained from PeproTech. LPS from dell’Istruzione dell’Universita`e della Ricerca (Fondo Investimenti Ricerca di Base, Escherichia coli (serotype 055:B5) was obtained from Sigma-Aldrich. Abs Progetto di Rilevante Interesse Nazionale, and Consiglio Nazionale delle Ricerche were purchased from Serotec, unless specified. Human cytokines were funding), Fondo Interno per la Ricerca Scientifica e Tecnologica (FIRST Project), measured using commercial ELISA kits purchased from R&D Systems, Ministero della Salute, Fondazione Cariplo (NOBEL Project), and the European according to the manufacturer’s instructions. All chemicals were obtained Commission (Innochem Project, FP6-518167; Mugen Project, LSHG-CT-2005- from Sigma-Aldrich, unless specified. 005203). F.O.M. is a recipient of the International PhD program in Cellular and Molecular Biology fellowship from Vita-Salute San Raffaele University. Cell preparation 2 Address correspondence and reprint requests to Dr. Massimo Locati, Istituto Clinico Humanitas, Via Manzoni 56, I-20089 Rozzano, Italy. E-mail address: massimo. Human monocytes were obtained from normal blood donor buffy coats by [email protected] two-step gradient centrifugation followed by an additional step using the Copyright © 2006 by The American Association of Immunologists, Inc. 0022-1767/06/$02.00 7304 TRANSCRIPTIONAL PROFILING OF MACROPHAGE DIFFERENTIATION FIGURE 1. PCA of the transcriptome expressed during macrophage differentiation and polarization. PCA was carried on all genes under in- Downloaded from vestigation to determine expression trends within the data set. Sample trend during maturation and polarization is shown in a scatter plot of the prin- FIGURE 2. K-mean clustering of genes differentially expressed during cipal components 1 and 2, which summarize 98% of the system variance. macrophage differentiation and polarization. Modulated genes were organized Bars represent the SD within the three donors studied. F, monocytes (Mo); by K-means clustering. The x-axis corresponds to the experimental conditions, U, monocytes after 3 days of culture with M-CSF (Md3); E, macrophages the y-axis to expression levels. Each line represents a gene, with red and green after 7 days of culture with M-CSF (M␾); Œ, M1-polarized macrophages for high and low expression levels, respectively. Monocyte differentiation cor- (M1); ‚, M2-polarized macrophages (M2). http://www.jimmunol.org/ related with a cluster on early affected genes (A, 478 genes) and a cluster of late affected genes (B, 390 genes). Two clusters (D, 1108 genes; E, 945 genes) are associated with M1 polarization, and one cluster (F, 104 genes) with M2 po- Monocyte Isolation kit II (Miltenyi Biotec) as previously described (17). larization. C (505 genes) includes genes with a complex behavior not directly ϩ Macrophages were obtained by culturing monocytes (98% CD14 , 13% linked to a specific cell differentiation
Load more

Recommended publications
  • PARSANA-DISSERTATION-2020.Pdf
    DECIPHERING TRANSCRIPTIONAL PATTERNS OF GENE REGULATION: A COMPUTATIONAL APPROACH by Princy Parsana A dissertation submitted to The Johns Hopkins University in conformity with the requirements for the degree of Doctor of Philosophy Baltimore, Maryland July, 2020 © 2020 Princy Parsana All rights reserved Abstract With rapid advancements in sequencing technology, we now have the ability to sequence the entire human genome, and to quantify expression of tens of thousands of genes from hundreds of individuals. This provides an extraordinary opportunity to learn phenotype relevant genomic patterns that can improve our understanding of molecular and cellular processes underlying a trait. The high dimensional nature of genomic data presents a range of computational and statistical challenges. This dissertation presents a compilation of projects that were driven by the motivation to efficiently capture gene regulatory patterns in the human transcriptome, while addressing statistical and computational challenges that accompany this data. We attempt to address two major difficulties in this domain: a) artifacts and noise in transcriptomic data, andb) limited statistical power. First, we present our work on investigating the effect of artifactual variation in gene expression data and its impact on trans-eQTL discovery. Here we performed an in-depth analysis of diverse pre-recorded covariates and latent confounders to understand their contribution to heterogeneity in gene expression measurements. Next, we discovered 673 trans-eQTLs across 16 human tissues using v6 data from the Genotype Tissue Expression (GTEx) project. Finally, we characterized two trait-associated trans-eQTLs; one in Skeletal Muscle and another in Thyroid. Second, we present a principal component based residualization method to correct gene expression measurements prior to reconstruction of co-expression networks.
    [Show full text]
  • Hsp70 and NF-Kb Mediated Control of Innate Inflammatory Responses In
    International Journal of Molecular Sciences Article Hsp70 and NF-kB Mediated Control of Innate Inflammatory Responses in a Canine Macrophage Cell Line Qingkang Lyu 1, Magdalena Wawrzyniuk 1, Victor P. M. G. Rutten 1,2 , Willem van Eden 1, Alice J. A. M. Sijts 1 and Femke Broere 1,* 1 Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, 3584 CL Utrecht, The Netherlands; [email protected] (Q.L.); [email protected] (M.W.); [email protected] (V.P.M.G.R.); [email protected] (W.v.E.); [email protected] (A.J.A.M.S.) 2 Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, 0110 Pretoria, South Africa * Correspondence: [email protected] Received: 15 July 2020; Accepted: 2 September 2020; Published: 4 September 2020 Abstract: The pathogenesis of many inflammatory diseases is associated with the uncontrolled activation of nuclear factor kappa B (NF-κB) in macrophages. Previous studies have shown that in various cell types, heat shock protein 70 (Hsp70) plays a crucial role in controlling NF-κB activity. So far, little is known about the role of Hsp70 in canine inflammatory processes. In this study we investigated the potential anti-inflammatory effects of Hsp70 in canine macrophages as well as the mechanisms underlying these effects. To this end, a canine macrophage cell line was stressed with arsenite, a chemical stressor, which upregulated Hsp70 expression as detected by flow cytometry and qPCR. A gene-edited version of this macrophage cell line lacking inducible Hsp70 was generated using CRISPR-Cas9 technology.
    [Show full text]
  • SLC2A6 Mouse Monoclonal Antibody [Clone ID: OTI7E3] Product Data
    OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TA500639 SLC2A6 Mouse Monoclonal Antibody [Clone ID: OTI7E3] Product data: Product Type: Primary Antibodies Clone Name: OTI7E3 Applications: IF, IHC, WB Recommend Dilution: IHC 1:200, WB: 1:200 Reactivity: Human Host: Mouse Isotype: IgG2a Clonality: Monoclonal Immunogen: Full-length protein expressed in 293T cell transfected with human SLC2A6 expression vector Formulation: PBS (pH 7.3) containing 1% BSA, 50% glycerol and 0.02% sodium azide. Concentration: 1.47 mg/ml Purification: Purified from mouse ascites fluids or tissue culture supernatant by affinity chromatography (protein A/G) Predicted Protein Size: 54.5 kDa Gene Name: solute carrier family 2 member 6 Database Link: NP_060055 Entrez Gene 11182 Human Background: Hexose transport into mammalian cells is catalyzed by a family of membrane proteins, including SLC2A6, that contain 12 transmembrane domains and a number of critical conserved residues. Synonyms: GLUT6; GLUT9; HSA011372 Protein Families: Transmembrane This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2020 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 4 SLC2A6 Mouse Monoclonal Antibody [Clone ID: OTI7E3] – TA500639 Product images: HEK293T cells were transfected with the pCMV6- ENTRY control (Left lane) or pCMV6-ENTRY SLC2A6 ([RC204391], Right lane) cDNA for 48 hrs and lysed. Equivalent amounts of cell lysates (5 ug per lane) were separated by SDS-PAGE and immunoblotted with anti-SLC2A6.
    [Show full text]
  • Viewed Under 23 (B) Or 203 (C) fi M M Male Cko Mice, and Largely Unaffected Magni Cation; Scale Bars, 500 M (B) and 50 M (C)
    BRIEF COMMUNICATION www.jasn.org Renal Fanconi Syndrome and Hypophosphatemic Rickets in the Absence of Xenotropic and Polytropic Retroviral Receptor in the Nephron Camille Ansermet,* Matthias B. Moor,* Gabriel Centeno,* Muriel Auberson,* † † ‡ Dorothy Zhang Hu, Roland Baron, Svetlana Nikolaeva,* Barbara Haenzi,* | Natalya Katanaeva,* Ivan Gautschi,* Vladimir Katanaev,*§ Samuel Rotman, Robert Koesters,¶ †† Laurent Schild,* Sylvain Pradervand,** Olivier Bonny,* and Dmitri Firsov* BRIEF COMMUNICATION *Department of Pharmacology and Toxicology and **Genomic Technologies Facility, University of Lausanne, Lausanne, Switzerland; †Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, Massachusetts; ‡Institute of Evolutionary Physiology and Biochemistry, St. Petersburg, Russia; §School of Biomedicine, Far Eastern Federal University, Vladivostok, Russia; |Services of Pathology and ††Nephrology, Department of Medicine, University Hospital of Lausanne, Lausanne, Switzerland; and ¶Université Pierre et Marie Curie, Paris, France ABSTRACT Tight control of extracellular and intracellular inorganic phosphate (Pi) levels is crit- leaves.4 Most recently, Legati et al. have ical to most biochemical and physiologic processes. Urinary Pi is freely filtered at the shown an association between genetic kidney glomerulus and is reabsorbed in the renal tubule by the action of the apical polymorphisms in Xpr1 and primary fa- sodium-dependent phosphate transporters, NaPi-IIa/NaPi-IIc/Pit2. However, the milial brain calcification disorder.5 How- molecular identity of the protein(s) participating in the basolateral Pi efflux remains ever, the role of XPR1 in the maintenance unknown. Evidence has suggested that xenotropic and polytropic retroviral recep- of Pi homeostasis remains unknown. Here, tor 1 (XPR1) might be involved in this process. Here, we show that conditional in- we addressed this issue in mice deficient for activation of Xpr1 in the renal tubule in mice resulted in impaired renal Pi Xpr1 in the nephron.
    [Show full text]
  • Complementary DNA Microarray Analysis of Chemokines and Their Receptors in Allergic Rhinitis RX Zhang,1 SQ Yu,2 JZ Jiang,3 GJ Liu3
    RX Zhang, et al ORIGINAL ARTICLE Complementary DNA Microarray Analysis of Chemokines and Their Receptors in Allergic Rhinitis RX Zhang,1 SQ Yu,2 JZ Jiang,3 GJ Liu3 1 Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai, China 2 Department of Otolaryngology , Jinan General Hospital of PLA, Shandong, China 3 Department of Otolaryngology, Changhai Hospital, Second Military Medical University, Shanghai, China ■ Abstract Objective: To analyze the roles of chemokines and their receptors in the pathogenesis of allergic rhinitis by observing the complementary DNA (cDNA) expression of the chemokines and their receptors in the nasal mucosa of patients with and without allergic rhinitis, using gene chips. Methods: The total RNAs were isolated from the nasal mucosa of 20 allergic rhinitis patients and purifi ed to messenger RNAs, and then reversely transcribed to cDNAs and incorporated with samples of fl uorescence-labeled with Cy5-dUPT (rhinitis patient samples) or Cy3- dUTP (control samples of nonallergic nasal mucosa). Thirty-nine cDNAs of chemokines and their receptors were latticed into expression profi le chips, which were hybridized with probes and then scanned with the computer to study gene expression according to the different fl uorescence intensities. Results: The cDNAs of the following chemokines were upregulated: CCL1, CCL2, CCL5, CCL7, CCL8, CCL11, CCL13, CCL14, CCL17, CCL18, CCL19, CCL24, and CX3CL1 in most of the allergic rhinitis sample chips. CCR2, CCR3, CCR4, CCR5, CCR8 and CX3CR1 were the highly expressed receptor genes. Low expression of CXCL4 was found in these tissues. Conclusion: The T helper cell (TH) immune system is not well regulated in allergic rhinitis.
    [Show full text]
  • Downloaded from GEO
    bioRxiv preprint doi: https://doi.org/10.1101/2020.08.17.252007; this version posted November 3, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. Oxylipin metabolism is controlled by mitochondrial b-oxidation during bacterial inflammation. Mariya Misheva1, Konstantinos Kotzamanis1*, Luke C Davies1*, Victoria J Tyrrell1, Patricia R S Rodrigues1, Gloria A Benavides2, Christine Hinz1, Robert C Murphy3, Paul Kennedy4, Philip R Taylor1,5, Marcela Rosas1, Simon A Jones1, Sumukh Deshpande1, Robert Andrews1, Magdalena A Czubala1, Mark Gurney1, Maceler Aldrovandi1, Sven W Meckelmann1, Peter Ghazal1, Victor Darley-Usmar2, Daniel White1, and Valerie B O’Donnell1 1Systems Immunity Research Institute and Division of Infection and Immunity, and School of Medicine, Cardiff University, UK, 2Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA, 3Department of Pharmacology, University of Colorado Denver, Aurora, CO 80045, USA, 4Cayman Chemical 1180 E Ellsworth Rd, Ann Arbor, MI 48108, United States, 5UK Dementia Research Institute at Cardiff, Cardiff University, UK Address correspondence: Valerie O’Donnell, [email protected] or Daniel White, [email protected], Systems Immunity Research Institute, Cardiff University *Both authors contributed equally to the study 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.17.252007; this version posted November 3, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.
    [Show full text]
  • Edinburgh Research Explorer
    Edinburgh Research Explorer International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list Citation for published version: Davenport, AP, Alexander, SPH, Sharman, JL, Pawson, AJ, Benson, HE, Monaghan, AE, Liew, WC, Mpamhanga, CP, Bonner, TI, Neubig, RR, Pin, JP, Spedding, M & Harmar, AJ 2013, 'International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands', Pharmacological reviews, vol. 65, no. 3, pp. 967-86. https://doi.org/10.1124/pr.112.007179 Digital Object Identifier (DOI): 10.1124/pr.112.007179 Link: Link to publication record in Edinburgh Research Explorer Document Version: Publisher's PDF, also known as Version of record Published In: Pharmacological reviews Publisher Rights Statement: U.S. Government work not protected by U.S. copyright General rights Copyright for the publications made accessible via the Edinburgh Research Explorer is retained by the author(s) and / or other copyright owners and it is a condition of accessing these publications that users recognise and abide by the legal requirements associated with these rights. Take down policy The University of Edinburgh has made every reasonable effort to ensure that Edinburgh Research Explorer content complies with UK legislation. If you believe that the public display of this file breaches copyright please contact [email protected] providing details, and we will remove access to the work immediately and investigate your claim. Download date: 02. Oct. 2021 1521-0081/65/3/967–986$25.00 http://dx.doi.org/10.1124/pr.112.007179 PHARMACOLOGICAL REVIEWS Pharmacol Rev 65:967–986, July 2013 U.S.
    [Show full text]
  • The Expression of the Human Apolipoprotein Genes and Their Regulation by Ppars
    CORE Metadata, citation and similar papers at core.ac.uk Provided by UEF Electronic Publications The expression of the human apolipoprotein genes and their regulation by PPARs Juuso Uski M.Sc. Thesis Biochemistry Department of Biosciences University of Kuopio June 2008 Abstract The expression of the human apolipoprotein genes and their regulation by PPARs. UNIVERSITY OF KUOPIO, the Faculty of Natural and Environmental Sciences, Curriculum of Biochemistry USKI Juuso Oskari Thesis for Master of Science degree Supervisors Prof. Carsten Carlberg, Ph.D. Merja Heinäniemi, Ph.D. June 2008 Keywords: nuclear receptors; peroxisome proliferator-activated receptor; PPAR response element; apolipoprotein; lipid metabolism; high density lipoprotein; low density lipoprotein. Lipids are any fat-soluble, naturally-occurring molecules and one of their main biological functions is energy storage. Lipoproteins carry hydrophobic lipids in the water and salt-based blood environment for processing and energy supply in liver and other organs. In this study, the genomic area around the apolipoprotein genes was scanned in silico for PPAR response elements (PPREs) using the in vitro data-based computer program. Several new putative REs were found in surroundings of multiple lipoprotein genes. The responsiveness of those apolipoprotein genes to the PPAR ligands GW501516, rosiglitazone and GW7647 in the HepG2, HEK293 and THP-1 cell lines were tested with real-time PCR. The APOA1, APOA2, APOB, APOD, APOE, APOF, APOL1, APOL3, APOL5 and APOL6 genes were found to be regulated by PPARs in direct or secondary manners. Those results provide new insights in the understanding of lipid metabolism and so many lifestyle diseases like atherosclerosis, type 2 diabetes, heart disease and stroke.
    [Show full text]
  • CD56+ T-Cells in Relation to Cytomegalovirus in Healthy Subjects and Kidney Transplant Patients
    CD56+ T-cells in Relation to Cytomegalovirus in Healthy Subjects and Kidney Transplant Patients Institute of Infection and Global Health Department of Clinical Infection, Microbiology and Immunology Thesis submitted in accordance with the requirements of the University of Liverpool for the degree of Doctor in Philosophy by Mazen Mohammed Almehmadi December 2014 - 1 - Abstract Human T cells expressing CD56 are capable of tumour cell lysis following activation with interleukin-2 but their role in viral immunity has been less well studied. The work described in this thesis aimed to investigate CD56+ T-cells in relation to cytomegalovirus infection in healthy subjects and kidney transplant patients (KTPs). Proportions of CD56+ T cells were found to be highly significantly increased in healthy cytomegalovirus-seropositive (CMV+) compared to cytomegalovirus-seronegative (CMV-) subjects (8.38% ± 0.33 versus 3.29%± 0.33; P < 0.0001). In donor CMV-/recipient CMV- (D-/R-)- KTPs levels of CD56+ T cells were 1.9% ±0.35 versus 5.42% ±1.01 in D+/R- patients and 5.11% ±0.69 in R+ patients (P 0.0247 and < 0.0001 respectively). CD56+ T cells in both healthy CMV+ subjects and KTPs expressed markers of effector memory- RA T-cells (TEMRA) while in healthy CMV- subjects and D-/R- KTPs the phenotype was predominantly that of naïve T-cells. Other surface markers, CD8, CD4, CD58, CD57, CD94 and NKG2C were expressed by a significantly higher proportion of CD56+ T-cells in healthy CMV+ than CMV- subjects. Functional studies showed levels of pro-inflammatory cytokines IFN-γ and TNF-α, as well as granzyme B and CD107a were significantly higher in CD56+ T-cells from CMV+ than CMV- subjects following stimulation with CMV antigens.
    [Show full text]
  • Macrophage Polarization in Response to Wear Particles in Vitro
    Cellular & Molecular Immunology (2013) 10, 471–482 ß 2013 CSI and USTC. All rights reserved 1672-7681/13 $32.00 www.nature.com/cmi RESEARCH ARTICLE Macrophage polarization in response to wear particles in vitro Joseph K Antonios, Zhenyu Yao, Chenguang Li, Allison J Rao and Stuart B Goodman Total joint replacement is a highly successful surgical procedure for treatment of patients with disabling arthritis and joint dysfunction. However, over time, with high levels of activity and usage of the joint, implant wear particles are generated from the articulating surfaces. These wear particles can lead to activation of an inflammatory reaction, and subsequent bone resorption around the implant (periprosthetic osteolysis). Cells of the monocyte/macrophage lineage orchestrate this chronic inflammatory response, which is dominated by a pro-inflammatory (M1) macrophage phenotype rather than an anti-inflammatory pro-tissue healing (M2) macrophage phenotype. While it has been shown that interleukin-4 (IL-4) selectively polarizes macrophages towards an M2 anti-inflammatory phenotype which promotes bone healing, rather than inflammation, little is known about the time course in which this occurs or conditions in which repolarization through IL-4 is most effective. The goal of this work was to study the time course of murine macrophage polarization and cytokine release in response to challenge with combinations of polymethyl methacrylate (PMMA) particles, lipopolysaccharide (LPS) and IL-4 in vitro. Treatment of particle-challenged monocyte/macrophages with IL-4 led to an initial suppression of pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) production and subsequent polarization into an M2 anti-inflammatory phenotype.
    [Show full text]
  • Genomic Selection Signatures in Sheep from the Western Pyrenees Otsanda Ruiz-Larrañaga, Jorge Langa, Fernando Rendo, Carmen Manzano, Mikel Iriondo, Andone Estonba
    Genomic selection signatures in sheep from the Western Pyrenees Otsanda Ruiz-Larrañaga, Jorge Langa, Fernando Rendo, Carmen Manzano, Mikel Iriondo, Andone Estonba To cite this version: Otsanda Ruiz-Larrañaga, Jorge Langa, Fernando Rendo, Carmen Manzano, Mikel Iriondo, et al.. Genomic selection signatures in sheep from the Western Pyrenees. Genetics Selection Evolution, BioMed Central, 2018, 50 (1), pp.9. 10.1186/s12711-018-0378-x. hal-02405217 HAL Id: hal-02405217 https://hal.archives-ouvertes.fr/hal-02405217 Submitted on 11 Dec 2019 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Distributed under a Creative Commons Attribution| 4.0 International License Ruiz-Larrañaga et al. Genet Sel Evol (2018) 50:9 https://doi.org/10.1186/s12711-018-0378-x Genetics Selection Evolution RESEARCH ARTICLE Open Access Genomic selection signatures in sheep from the Western Pyrenees Otsanda Ruiz‑Larrañaga1* , Jorge Langa1, Fernando Rendo2, Carmen Manzano1, Mikel Iriondo1 and Andone Estonba1 Abstract Background: The current large spectrum of sheep phenotypic diversity
    [Show full text]
  • The Flagellar Arginine Kinase in Trypanosoma Brucei Is Important for Infection in Tsetse Flies
    RESEARCH ARTICLE The Flagellar Arginine Kinase in Trypanosoma brucei Is Important for Infection in Tsetse Flies Cher-Pheng Ooi1¤, Brice Rotureau1, Simonetta Gribaldo2, Christina Georgikou1, Daria Julkowska1, Thierry Blisnick1, Sylvie Perrot1, Ines Subota1, Philippe Bastin1* 1 Trypanosome Cell Biology Unit, INSERM U1201, Institut Pasteur, 25 Rue du Docteur Roux, 75015, Paris, France, 2 Molecular Biology of Gene in Extremophiles Unit, Department of Microbiology, Institut Pasteur, 25 rue du Docteur Roux, 75015, Paris, France ¤ Current address: Department of Life Sciences, Sir Alexander Fleming Building, Imperial College-South Kensington, London, SW7 2AZ, United Kingdom * [email protected] Abstract OPEN ACCESS African trypanosomes are flagellated parasites that cause sleeping sickness. Parasites are Citation: Ooi C-P, Rotureau B, Gribaldo S, Georgikou C, Julkowska D, Blisnick T, et al. (2015) transmitted from one mammalian host to another by the bite of a tsetse fly. Trypanosoma The Flagellar Arginine Kinase in Trypanosoma brucei brucei possesses three different genes for arginine kinase (AK) including one (AK3) that Is Important for Infection in Tsetse Flies. PLoS ONE encodes a protein localised to the flagellum. AK3 is characterised by the presence of a 10(7): e0133676. doi:10.1371/journal.pone.0133676 unique amino-terminal insertion that specifies flagellar targeting. We show here a phyloge- Editor: Frank Voncken, University of Hull, UNITED netic analysis revealing that flagellar AK arose in two independent duplication events in KINGDOM T. brucei and T. congolense, the two species of African trypanosomes that infect the tsetse Received: April 11, 2015 midgut. In T. brucei, AK3 is detected in all stages of parasite development in the fly (in the Accepted: June 29, 2015 midgut and in the salivary glands) as well as in bloodstream cells, but with predominance at Published: July 28, 2015 insect stages.
    [Show full text]