Pathogen Induction of CXCR4/TLR2 Cross-Talk Impairs Host Defense Function
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TLR3-Dependent Activation of TLR2 Endogenous Ligands Via the Myd88 Signaling Pathway Augments the Innate Immune Response
cells Article TLR3-Dependent Activation of TLR2 Endogenous Ligands via the MyD88 Signaling Pathway Augments the Innate Immune Response 1 2, 1 3 Hellen S. Teixeira , Jiawei Zhao y, Ethan Kazmierski , Denis F. Kinane and Manjunatha R. Benakanakere 2,* 1 Department of Orthodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19004, USA; [email protected] (H.S.T.); [email protected] (E.K.) 2 Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19004, USA; [email protected] 3 Periodontology Department, Bern Dental School, University of Bern, 3012 Bern, Switzerland; [email protected] * Correspondence: [email protected] Present address: Department of Pathology, Wayne State University School of Medicine, y 541 East Canfield Ave., Scott Hall 9215, Detroit, MI 48201, USA. Received: 30 June 2020; Accepted: 12 August 2020; Published: 17 August 2020 Abstract: The role of the adaptor molecule MyD88 is thought to be independent of Toll-like receptor 3 (TLR3) signaling. In this report, we demonstrate a previously unknown role of MyD88 in TLR3 signaling in inducing endogenous ligands of TLR2 to elicit innate immune responses. Of the various TLR ligands examined, the TLR3-specific ligand polyinosinic:polycytidylic acid (poly I:C), significantly induced TNF production and the upregulation of other TLR transcripts, in particular, TLR2. Accordingly, TLR3 stimulation also led to a significant upregulation of endogenous TLR2 ligands mainly, HMGB1 and Hsp60. By contrast, the silencing of TLR3 significantly downregulated MyD88 and TLR2 gene expression and pro-inflammatory IL1β, TNF, and IL8 secretion. The silencing of MyD88 similarly led to the downregulation of TLR2, IL1β, TNF and IL8, thus suggesting MyD88 / to somehow act downstream of TLR3. -
Galectin-4 Interaction with CD14 Triggers the Differentiation of Monocytes Into Macrophage-Like Cells Via the MAPK Signaling Pathway
Immune Netw. 2019 Jun;19(3):e17 https://doi.org/10.4110/in.2019.19.e17 pISSN 1598-2629·eISSN 2092-6685 Original Article Galectin-4 Interaction with CD14 Triggers the Differentiation of Monocytes into Macrophage-like Cells via the MAPK Signaling Pathway So-Hee Hong 1,2,3,4,5, Jun-Seop Shin 1,2,3,5, Hyunwoo Chung 1,2,4,5, Chung-Gyu Park 1,2,3,4,5,* 1Xenotransplantation Research Center, Seoul National University College of Medicine, Seoul 03080, Korea 2Institute of Endemic Diseases, Seoul National University College of Medicine, Seoul 03080, Korea 3Cancer Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea 4Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea 5Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul 03080, Korea Received: Jan 28, 2019 ABSTRACT Revised: May 13, 2019 Accepted: May 19, 2019 Galectin-4 (Gal-4) is a β-galactoside-binding protein mostly expressed in the gastrointestinal *Correspondence to tract of animals. Although intensive functional studies have been done for other galectin Chung-Gyu Park isoforms, the immunoregulatory function of Gal-4 still remains ambiguous. Here, we Department of Microbiology and Immunology, Seoul National University College of Medicine, demonstrated that Gal-4 could bind to CD14 on monocytes and induce their differentiation 103 Daehak-ro, Jongno-gu, Seoul 03080, into macrophage-like cells through the MAPK signaling pathway. Gal-4 induced the phenotypic Korea. changes on monocytes by altering the expression of various surface molecules, and induced E-mail: [email protected] functional changes such as increased cytokine production and matrix metalloproteinase expression and reduced phagocytic capacity. -
IL21R Expressing CD14+CD16+ Monocytes Expand in Multiple
Plasma Cell Disorders SUPPLEMENTARY APPENDIX IL21R expressing CD14 +CD16 + monocytes expand in multiple myeloma patients leading to increased osteoclasts Marina Bolzoni, 1 Domenica Ronchetti, 2,3 Paola Storti, 1,4 Gaetano Donofrio, 5 Valentina Marchica, 1,4 Federica Costa, 1 Luca Agnelli, 2,3 Denise Toscani, 1 Rosanna Vescovini, 1 Katia Todoerti, 6 Sabrina Bonomini, 7 Gabriella Sammarelli, 1,7 Andrea Vecchi, 8 Daniela Guasco, 1 Fabrizio Accardi, 1,7 Benedetta Dalla Palma, 1,7 Barbara Gamberi, 9 Carlo Ferrari, 8 Antonino Neri, 2,3 Franco Aversa 1,4,7 and Nicola Giuliani 1,4,7 1Myeloma Unit, Dept. of Medicine and Surgery, University of Parma; 2Dept. of Oncology and Hemato-Oncology, University of Milan; 3Hematology Unit, “Fondazione IRCCS Ca’ Granda”, Ospedale Maggiore Policlinico, Milan; 4CoreLab, University Hospital of Parma; 5Dept. of Medical-Veterinary Science, University of Parma; 6Laboratory of Pre-clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, Rionero in Vulture; 7Hematology and BMT Center, University Hospital of Parma; 8Infectious Disease Unit, University Hospital of Parma and 9“Dip. Oncologico e Tecnologie Avanzate”, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Italy ©2017 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol. 2016.153841 Received: August 5, 2016. Accepted: December 23, 2016. Pre-published: January 5, 2017. Correspondence: [email protected] SUPPLEMENTAL METHODS Immunophenotype of BM CD14+ in patients with monoclonal gammopathies. Briefly, 100 μl of total BM aspirate was incubated in the dark with anti-human HLA-DR-PE (clone L243; BD), anti-human CD14-PerCP-Cy 5.5, anti-human CD16-PE-Cy7 (clone B73.1; BD) and anti-human CD45-APC-H 7 (clone 2D1; BD) for 20 min. -
Identification of 18 Immune Cell Subsets Using 13-Color Panel
Immunophenotyping Identification of 18 immune cell subsets in human blood using a 13-color panel Background Cell type Function Phenotype Flow cytometry has become the method of choice for Eosinophils Parasitic immunity CD45+, SSCmid/hi, CD14 –, CD16 –, CD19– immunophenotyping and identifying specific cellular + mid/hi subsets. Within seconds, it provides a thorough overview of Neutrophils Innate Immunity CD45 , SSC , CD14 –, CD16+, CD19– the major cell types that constitute a sample. Using multiple + mid markers simultaneously increases the number of parameters Classical Phagocytosis of CD45 , SSC , monocytes pathogens and CD14+, CD16– that can be analyzed per run and decreases the amount of antigen presentation starting material required to perform an assay. This can be Intermediate Phagocytosis of CD45+, SSCmid, critical for precious sample material and long-term immune- monocytes pathogens and CD14+, CD16mid monitoring studies. In this application note, we demonstrate antigen presentation 13-color immunophenotyping of human peripheral blood Non-classical Phagocytosis of CD45+, SSCmid, + + mononuclear cells (PBMCs) using the MACSQuant® Analyzer 16, monocytes pathogens and CD14 , CD16 antigen presentation a compact and reliable benchtop flow cytometer equipped + low + with three lasers. The markers selected allow for the Class-switched Adaptive immunity CD45 , SSC , CD19 , memory B cells CD27+, IgD–, CD14– simultaneous identification and analysis of 18 different cell Non-switched Adaptive immunity CD45+, SSClow, CD19+, populations, thus maximizing the amount of information that memory B cells CD27+, IgD+, CD14– can be retrieved from the sample material analyzed. This is Naive B cells Adaptive immunity – CD45+, SSClow, CD19+, critical when input material is limited, as is often the case for non-antigen CD27–, IgD+, CD14– pediatric or disease studies. -
Maturation and Is Inhibited by TLR2 Signaling Through TLR4 Promotes
Role of TLR in B Cell Development: Signaling through TLR4 Promotes B Cell Maturation and Is Inhibited by TLR2 This information is current as Elize A. Hayashi, Shizuo Akira and Alberto Nobrega of September 28, 2021. J Immunol 2005; 174:6639-6647; ; doi: 10.4049/jimmunol.174.11.6639 http://www.jimmunol.org/content/174/11/6639 Downloaded from References This article cites 45 articles, 26 of which you can access for free at: http://www.jimmunol.org/content/174/11/6639.full#ref-list-1 Why The JI? Submit online. http://www.jimmunol.org/ • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average by guest on September 28, 2021 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 © 2005 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Role of TLR in B Cell Development: Signaling through TLR4 Promotes B Cell Maturation and Is Inhibited by TLR21 Elize A. Hayashi,* Shizuo Akira,† and Alberto Nobrega2* The role of TLR4 in mature B cell activation is well characterized. -
Combined Carriership of TLR9 -1237C and CD14 -260T Alleles Enhances the Risk of Developing Chronic Relapsing Pouchitis
CORE Metadata, citation and similar papers at core.ac.uk Provided by DSpace at VU PO Box 2345, Beijing 100023, China World J Gastroenterol 2005;11(46):7323-7329 www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327 [email protected] © 2005 The WJG Press and Elsevier Inc. All rights reserved. ELSEVIER • RAPID COMMUNICATION • Combined carriership of TLR9 -1237C and CD14 -260T alleles enhances the risk of developing chronic relapsing pouchitis KM Lammers, S Ouburg, SA Morré, JBA Crusius, P Gionchetti, F Rizzello, C Morselli, E Caramelli, R Conte, G Poggioli, M Campieri, AS Peña KM Lammers, P Gionchetti, F Rizzello, C Morselli, M CONCLUSION: There is no evidence that the SNPs Campieri, Department of Internal Medicine and Gastroenterology, predispose to the need for IPAA surgery. The signifi cant Policlinico S. Orsola, University of Bologna, Bologna, Italy increase of the combined carriership of the CD14 S Ouburg, SA Morré, JBA Crusius, AS Peña, Laboratory of -260T and TLR9 -1237C alleles in the chronic relapsing Immunogenetics, VU University Medical Center, Amsterdam, The pouchitis group suggests that these markers identify Netherlands a subgroup of IPAA patients with a risk of developing E Caramelli, Institute of Histology and General Embryology, University of Bologna, Bologna, Italy chronic or refractory pouchitis. R Conte, Department of Immunohaematology and Blood Transfusion, Policlinico S. Orsola, University of Bologna, © 2005 The WJG Press and Elsevier Inc. All rights reserved. Bologna, Italy AS Peña, Laboratory of Immunogenetics and Department of Key words: Pouchitis; Innate immunity; Single nucleotide Gastroenterology, VU University Medical Center, Amsterdam, polymorphisms; CD14 ; TLR9 The Netherlands G Poggioli, Department of Surgery and Organ Transplantation, Lammers KM, Ouburg S, Morré SA, Crusius JBA, Gionchetti Policlinic S. -
TLR Signaling Pathways
Seminars in Immunology 16 (2004) 3–9 TLR signaling pathways Kiyoshi Takeda, Shizuo Akira∗ Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and ERATO, Japan Science and Technology Corporation, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan Abstract Toll-like receptors (TLRs) have been established to play an essential role in the activation of innate immunity by recognizing spe- cific patterns of microbial components. TLR signaling pathways arise from intracytoplasmic TIR domains, which are conserved among all TLRs. Recent accumulating evidence has demonstrated that TIR domain-containing adaptors, such as MyD88, TIRAP, and TRIF, modulate TLR signaling pathways. MyD88 is essential for the induction of inflammatory cytokines triggered by all TLRs. TIRAP is specifically involved in the MyD88-dependent pathway via TLR2 and TLR4, whereas TRIF is implicated in the TLR3- and TLR4-mediated MyD88-independent pathway. Thus, TIR domain-containing adaptors provide specificity of TLR signaling. © 2003 Elsevier Ltd. All rights reserved. Keywords: TLR; Innate immunity; Signal transduction; TIR domain 1. Introduction 2. Toll-like receptors Toll receptor was originally identified in Drosophila as an A mammalian homologue of Drosophila Toll receptor essential receptor for the establishment of the dorso-ventral (now termed TLR4) was shown to induce the expression pattern in developing embryos [1]. In 1996, Hoffmann and of genes involved in inflammatory responses [3]. In addi- colleagues demonstrated that Toll-mutant flies were highly tion, a mutation in the Tlr4 gene was identified in mouse susceptible to fungal infection [2]. This study made us strains that were hyporesponsive to lipopolysaccharide [4]. aware that the immune system, particularly the innate im- Since then, Toll receptors in mammals have been a major mune system, has a skilful means of detecting invasion by focus in the immunology field. -
Original Article Investigation for the Roles of TLR2, TLR9 and Th17/Treg in the Pathogenesis of Infectious Mononucleosis
Int J Clin Exp Med 2017;10(10):14946-14953 www.ijcem.com /ISSN:1940-5901/IJCEM0037168 Original Article Investigation for the roles of TLR2, TLR9 and Th17/Treg in the pathogenesis of infectious mononucleosis Aning Gao1, Yawang Shao2 1Department of Pediatrics, The Central Hospital of Xianyang, Shaanxi Province, China; 2Department of Pediatrics, The First People’ s Hospital of Xianyang, Xianyang City 712000, Shaanxi Province, China Received August 3, 2016; Accepted August 12, 2017; Epub October 15, 2017; Published October 30, 2017 Abstract: Infectious mononucleosis (IM) is caused by Epstein-Barr virus (EBV) infection. Toll-like receptor 2 (TLR2) has most recognized ligands, and is possibly direct receptor for anti-EBV. EBV can also activate TLR9 on B cells for inducing anti-viral response. T helper cell 17 (Th17) can promote inflammation by secreting IL-17, and is possibly involved in IM pathogenesis. Regulatory T cell (Treg) is a T cell sub-population with immune suppression. The previ- ous study has indicated insufficient Treg cell immunity for acute IM onset. This study thus aims to investigate the TLR2, TL9, Th17 and CD4+CD25+Treg cell expression, and to explore its potential role in IM. A total of 98 acute IM children and 76 IM children at recovery period were recruited in our hospital, in parallel with 52 healthy children. The qRT-PCR and western blot assay were used to test mRNA or protein expressions of TLR2 and TLR9, respectively. Flow cytometry was used to test percentage of Th17 and CD4+CD25+Foxp3+T cell in total CD4+T cells. ELISA was employed for detecting serum levels of IL-17, IL-22, IL-19 and TGF-β. -
TLR2 Signaling Pathway Combats Streptococcus Uberis Infection by Inducing Mitochondrial Reactive Oxygen Species Production
cells Article TLR2 Signaling Pathway Combats Streptococcus uberis Infection by Inducing Mitochondrial Reactive Oxygen Species Production 1, 1, 1 1,2 1 2 Bin Li y, Zhixin Wan y, Zhenglei Wang , Jiakun Zuo , Yuanyuan Xu , Xiangan Han , Vanhnaseng Phouthapane 3 and Jinfeng Miao 1,* 1 MOE Joint International Research Laboratory of Animal Health and Food Safty, Key Laboratory of Animal Physiology and Biochemistry, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China; [email protected] (B.L.); [email protected] (Z.W.); [email protected] (Z.W.); [email protected] (J.Z.); [email protected] (Y.X.) 2 Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai 200241, China; [email protected] 3 Biotechnology and Ecology Institute, Ministry of Science and Technology (MOST), Vientiane 22797, Laos; [email protected] * Correspondence: [email protected]; Fax: +86-25-8439-8669 These authors contributed equally to this work. y Received: 6 January 2020; Accepted: 19 February 2020; Published: 21 February 2020 Abstract: Mastitis caused by Streptococcus uberis (S. uberis) is a common and difficult-to-cure clinical disease in dairy cows. In this study, the role of Toll-like receptors (TLRs) and TLR-mediated signaling pathways in mastitis caused by S. uberis was investigated using mouse models and mammary / epithelial cells (MECs). We used S. uberis to infect mammary glands of wild type, TLR2− − and / TLR4− − mice and quantified the adaptor molecules in TLR signaling pathways, proinflammatory cytokines, tissue damage, and bacterial count. When compared with TLR4 deficiency, TLR2 deficiency induced more severe pathological changes through myeloid differentiation primary response 88 (MyD88)-mediated signaling pathways during S. -
Adjuvant Effect of the Novel TLR1/TLR2 Agonist Diprovocim Synergizes with Anti–PD-L1 to Eliminate Melanoma in Mice
Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti–PD-L1 to eliminate melanoma in mice Ying Wanga, Lijing Sua, Matthew D. Morinb, Brian T. Jonesb, Yuto Mifuneb, Hexin Shia, Kuan-wen Wanga, Xiaoming Zhana, Aijie Liua, Jianhui Wanga, Xiaohong Lia, Miao Tanga, Sara Ludwiga, Sara Hildebranda, Kejin Zhouc,d, Daniel J. Siegwartc,d, Eva Marie Y. Morescoa, Hong Zhanga, Dale L. Bogerb, and Bruce Beutlera,1 aCenter for the Genetics of Host Defense, University of Texas Southwestern Medical Center, Dallas, TX 75390; bDepartment of Chemistry, The Scripps Research Institute, La Jolla, CA 92037; cSimmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390; and dDepartment of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390 Edited by Dennis A. Carson, University of California, San Diego, La Jolla, CA, and approved July 2, 2018 (received for review June 28, 2018) Successful cancer immunotherapy entails activation of innate immune (MyD88,TRIF,TRAM,andMAL),kinases, and ubiquitin ligases receptors to promote dendritic cell (DC) maturation, antigen pre- to activate NF-κB and IRFs (12–14). These and other transcription sentation, up-regulation of costimulatory molecules, and cytokine factors induce the expression of thousands of genes that carry out secretion, leading to activation of tumor antigen-specific cytotoxic the innate immune response (15). Several nucleotide-based adju- T lymphocytes (CTLs). Here we screened a synthetic library of 100,000 vants such as TLR3 agonist poly I:C (9), TLR9 agonist CpG (16), compounds for innate immune activators using TNF production by and STING agonist cGAMP (6) have been reported to improve THP-1 cells as a readout. -
Cx3cr1 Mediates the Development of Monocyte-Derived Dendritic Cells During Hepatic Inflammation
CX3CR1 MEDIATES THE DEVELOPMENT OF MONOCYTE-DERIVED DENDRITIC CELLS DURING HEPATIC INFLAMMATION. Supplementary material Supplementary Figure 1: Liver CD45+ myeloid cells were pre-gated for Ly6G negative cells for excluding granulocytes and HDCs subsequently analyzed among the cells that were CD11c+ and had high expression of MHCII. Supplementary Table 1 low/- high + Changes in gene expression between CX3CR1 and CX3CR1 CD11b myeloid hepatic dendritic cells (HDCs) from CCl4-treated mice high Genes up-regulated in CX3CR1 HDCs Gene Fold changes P value Full name App 4,01702 5,89E-05 amyloid beta (A4) precursor protein C1qa 9,75881 1,69E-22 complement component 1, q subcomponent, alpha polypeptide C1qb 9,19882 3,62E-20 complement component 1, q subcomponent, beta polypeptide Ccl12 2,51899 0,011769 chemokine (C-C motif) ligand 12 Ccl2 6,53486 6,37E-11 chemokine (C-C motif) ligand 2 Ccl3 4,99649 5,84E-07 chemokine (C-C motif) ligand 3 Ccl4 4,42552 9,62E-06 chemokine (C-C motif) ligand 4 Ccl6 3,9311 8,46E-05 chemokine (C-C motif) ligand 6 Ccl7 2,60184 0,009272 chemokine (C-C motif) ligand 7 Ccl9 4,17294 3,01E-05 chemokine (C-C motif) ligand 9 Ccr2 3,35195 0,000802 chemokine (C-C motif) receptor 2 Ccr5 3,23358 0,001222 chemokine (C-C motif) receptor 5 Cd14 6,13325 8,61E-10 CD14 antigen Cd36 2,94367 0,003243 CD36 antigen Cd44 4,89958 9,60E-07 CD44 antigen Cd81 6,49623 8,24E-11 CD81 antigen Cd9 3,06253 0,002195 CD9 antigen Cdkn1a 4,65279 3,27E-06 cyclin-dependent kinase inhibitor 1A (P21) Cebpb 6,6083 3,89E-11 CCAAT/enhancer binding protein (C/EBP), -
Human TLR9 Confers Responsiveness to Bacterial DNA Via Species-Specific Cpg Motif Recognition
Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition Stefan Bauer*†‡, Carsten J. Kirschning*†, Hans Ha¨ cker*, Vanessa Redecke*, Susanne Hausmann*, Shizuo Akira§, Hermann Wagner*, and Grayson B. Lipford*‡ *Institute for Medical Microbiology, Immunology and Hygiene, Technical University of Munich, 81675 Munich, Germany; and §Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan Communicated by Johannes van Rood, Europdonor Foundation, Leiden, The Netherlands, June 11, 2001 (received for review February 2, 2001) The Toll-like receptor (TLR) family consists of phylogenetically human TLR9 (hTLR9) is correlated with CpG-DNA respon- conserved transmembrane proteins, which function as mediators siveness in primary human cells and that transfection of either of innate immunity for recognition of pathogen-derived ligands hTLR9 or mTLR9 into nonresponsive cells reconstitutes and subsequent cell activation via the Toll͞IL-1R signal pathway. MyD88-dependent CpG-DNA responses. Transfected hTLR9 Here, we show that human TLR9 (hTLR9) expression in human and mTLR9 required distinct CpG motifs for signal initiation, immune cells correlates with responsiveness to bacterial deoxy- implying they directly engage immunostimulatory CpG-DNA in cytidylate-phosphate-deoxyguanylate (CpG)-DNA. Notably ‘‘gain a species-specific manner. of function’’ to immunostimulatory CpG-DNA is achieved by ex- pressing TLR9 in human nonresponder cells. Transfection of either Materials and Methods human or murine TLR9 conferred responsiveness in a CD14- and Cells and Reagents. Human embryonic kidney 293 cells were from MD2-independent manner, yet required species-specific CpG-DNA ATCC. Peripheral blood mononuclear cells (PBMC), human B ϩ motifs for initiation of the Toll͞IL-1R signal pathway via MyD88.