Toll-Like Receptor 2 and Mincle Cooperatively Sense Corynebacterial Cell Wall Glycolipids

Judith Schick, Philipp Etschel, Rebeca Bailo, Lisa Ott, Apoorva Bhatt, Bernd Lepenies, Carsten Kirschning, Andreas Burkovski, Roland Lang

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Nontoxigenic Corynebacterium diphtheriae and Corynebacterium ulceranscause invasive disease in humans and animals. Host sensing of corynebacteria is largely uncharacterized, albeit the recognition of lipoglycans by Toll-like receptor 2 (TLR2) appears to be important for macrophage activation by corynebacteria. The members of the orderCorynebacterineae(e.g., mycobacteria, nocardia, and rhodococci) share a glycolipid-rich cell wall dominated by mycolic acids (termed corynomycolic acids in corynebacteria). The mycolic acid-containing cord factor of mycobacteria, trehalose dimycolate, activates the C-type lectin receptor (CLR) Mincle. Here, we show that glycolipid extracts from the cell walls of several pathogenic and nonpathogenicCorynebacteriumstrains directly bound to recombinant Minclein vitroMacrophages deficient in Mincle or its adapter protein Fc receptor gamma chain (FcRγ) produced severely reduced amounts of granulocyte colony-stimulating factor (G-CSF) and of nitric oxide (NO) upon challenge with corynebacterial glycolipids. Consistently, cell wall extracts of a particularC. diphtheriaestrain (DSM43989) lacking mycolic acid esters neither bound Mincle nor activated macrophages. Furthermore, TLR2 but not TLR4 was critical for sensing of cell wall extracts and whole corynebacteria. The upregulation of Mincle expression upon encountering corynebacteria required TLR2. Thus, macrophage activation by the corynebacterial cell wall relies on TLR2-driven robust Mincle expression and the cooperative action of both receptors.

Original languageEnglish
Article numbere00075-17
JournalInfection and Immunity
Issue number7
Early online date8 May 2017
Publication statusPublished - 1 Jul 2017


  • Animals
  • Cell Wall
  • Corynebacterium
  • Glycolipids
  • Granulocyte Colony-Stimulating Factor
  • Lectins, C-Type
  • Macrophages
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Nitric Oxide
  • Protein Binding
  • Toll-Like Receptor 2


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