The C-type lectin receptor Mincle binds to Streptococcus pneumoniae but plays a limited role in the anti-pneumococcal innate immune response

PLoS One. 2015 Feb 6;10(2):e0117022. doi: 10.1371/journal.pone.0117022. eCollection 2015.

Abstract

The innate immune system employs C-type lectin receptors (CLRs) to recognize carbohydrate structures on pathogens and self-antigens. The Macrophage-inducible C-type lectin (Mincle) is a FcRγ-coupled CLR that was shown to bind to mycobacterial cord factor as well as certain fungal species. However, since CLR functions during bacterial infections have not yet been investigated thoroughly, we aimed to examine their function in Streptococcus pneumonia infection. Binding studies using a library of recombinantly expressed CLR-Fc fusion proteins indicated a specific, Ca2+-dependent, and serotype-specific binding of Mincle to S. pneumonia. Subsequent experiments with different Mincle-expressing cells as well as Mincle-deficient mice, however, revealed a limited role of this receptor in bacterial phagocytosis, neutrophil-mediated killing, cytokine production, and antibacterial immune response during pneumonia. Collectively, our results indicate that Mincle is able to recognize S. pneumonia but is not required for the anti-pneumococcal innate immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cells, Immobilized / chemistry
  • Cells, Immobilized / metabolism
  • Cytokines / analysis
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Immunity, Innate*
  • Lectins, C-Type / deficiency
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism*
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / immunology
  • Phagocytosis
  • Pneumonia / pathology
  • Pneumonia / veterinary
  • Protein Binding
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Streptococcus pneumoniae / chemistry
  • Streptococcus pneumoniae / metabolism*

Substances

  • Clecsf8 protein, mouse
  • Cytokines
  • Lectins, C-Type
  • Membrane Proteins
  • Recombinant Fusion Proteins
  • Calcium

Grants and funding

This work was supported by the Deutsche Forschungsgemeinschaft (GRK1673/B5 to A.R., M.W. and B.O., OP 86/7-2 to M.W. and B.O., SFB/TR84 project C3/6 to M.W., project B1 to N.S., and project A1/A5 to B.O., SFB765 project B8 to P.H.S. and B.L., and SFB796 project B6 to R.L.). S.Z. and B.L. acknowledge funding by the IMPRS on Multiscale Bio-Systems. Funding by the German Federal Ministry of Education and Research (BMBF, Fkz. 0315446 to B.L. and 01ZX1304B to M.W.) is also gratefully acknowledged. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.