Deciphering the molecular basis of mycobacteria and lipoglycan recognition by the C-type lectin Dectin-2

Research output: Contribution to journalArticle

Authors

  • Alexiane Decout
  • Sandro Silva-Gomes
  • Daniel Drocourt
  • Emilyne Blattes
  • Michel Rivière
  • Jacques Prandi
  • Gérald Larrouy-Maumus
  • Anne-Marie Caminade
  • Beston Hamasur
  • Gunilla Källenius
  • Devinder Kaur
  • Karen M Dobos
  • Megan Lucas
  • Iain C Sutcliffe
  • Ben J Appelmelk
  • Martine Gilleron
  • Mary Jackson
  • Alain Vercellone
  • Gérard Tiraby
  • Jérôme Nigou

Colleges, School and Institutes

External organisations

  • Global Health Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
  • GlaxoSmithKline (GSK), Stevenage Herts, SG1 2NY, UK.
  • InvivoGen, Research Department, 31400, Toulouse, France.
  • Innovative Medecine for Tuberculosis (iM4TB), Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015, Lausanne, Switzerland.
  • Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier, 31077, Toulouse, France.
  • Medical Research Council Centre for Molecular Bacteriology and Infection, Imperial College London, London, SW7 2AZ, UK.
  • Laboratoire de Chimie de Coordination, Université de Toulouse, CNRS, Université Paul Sabatier, 31077, Toulouse, France.
  • Biopromic AB, 171 65, Solna, Sweden.
  • Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm SE-171 77, Sweden.
  • Massachusetts Supranational TB Reference Laboratory, University of Massachusetts Medical School, Jamaica Plain, MA, 0213, USA.
  • Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, 80523-1682, USA.
  • Northumbria University Newcastle
  • Institute of Microbiology and Infection, School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
  • Department of Medical Microbiology and Infection Control, VU University Medical Center, 1081 BT, Amsterdam, The Netherlands.
  • Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse, CNRS, Université Paul Sabatier, 31077, Toulouse, France. jerome.nigou@ipbs.fr.

Abstract

Dectin-2 is a C-type lectin involved in the recognition of several pathogens such as Aspergillus fumigatus, Candida albicans, Schistosoma mansonii, and Mycobacterium tuberculosis that triggers Th17 immune responses. Identifying pathogen ligands and understanding the molecular basis of their recognition is one of the current challenges. Purified M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) was shown to induce signaling via Dectin-2, an activity that requires the (α1 → 2)-linked mannosides forming the caps. Here, using isogenic M. tuberculosis mutant strains, we demonstrate that ManLAM is a bona fide and actually the sole ligand mediating bacilli recognition by Dectin-2, although M. tuberculosis produces a variety of cell envelope mannoconjugates, such as phosphatidyl-myo-inositol hexamannosides, lipomannan or manno(lipo)proteins, that bear (α1 → 2)-linked mannosides. In addition, we found that Dectin-2 can recognize lipoglycans from other bacterial species, such as Saccharotrix aerocolonigenes or the human opportunistic pathogen Tsukamurella paurometabola, suggesting that lipoglycans are prototypical Dectin-2 ligands. Finally, from a structure/function relationship perspective, we show, using lipoglycan variants and synthetic mannodendrimers, that dimannoside caps and multivalent interaction are required for ligand binding to and signaling via Dectin-2. Better understanding of the molecular basis of ligand recognition by Dectin-2 will pave the way for the rational design of potent adjuvants targeting this receptor.

Details

Original languageEnglish
Article number16840
JournalScientific Reports
Volume8
Issue number1
Publication statusPublished - 15 Nov 2018