C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia

Friederike Behler-Janbeck, Tomotsugu Takano, Regina Maus, Jennifer Stolper, Danny Jonigk, Meritxell Tort Tarrés, Thomas Fuehner, Antje Prasse, Tobias Welte, Mattie S.M. Timmer, Bridget L. Stocker, Yoichi Nakanishi, Tomofumi Miyamoto, Sho Yamasaki, Ulrich A. Maus

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Among various innate immune receptor families, the role of C-type lectin receptors (CLRs) in lung protective immunity against Streptococcus pneumoniae (S. pneumoniae) is not fully defined. We here show that Mincle gene expression was induced in alveolar macrophages and neutrophils in bronchoalveolar lavage fluids of mice and patients with pneumococcal pneumonia. Moreover, S. pneumoniae directly triggered Mincle reporter cell activation in vitro via its glycolipid glucosyl-diacylglycerol (Glc-DAG), which was identified as the ligand recognized by Mincle. Purified Glc-DAG triggered Mincle reporter cell activation and stimulated inflammatory cytokine release by human alveolar macrophages and alveolar macrophages from WT but not Mincle KO mice. Mincle deficiency led to increased bacterial loads and decreased survival together with strongly dysregulated cytokine responses in mice challenged with focal pneumonia inducing S. pneumoniae, all of which was normalized in Mincle KO mice reconstituted with a WT hematopoietic system. In conclusion, the Mincle-Glc-DAG axis is a hitherto unrecognized element of lung protective immunity against focal pneumonia induced by S. pneumoniae.

Original languageEnglish
Article numbere1006038
JournalPLoS pathogens
Volume12
Issue number12
DOIs
Publication statusPublished - Dec 6 2016

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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