PLoS Pathog. 2016 Dec 6;12(12):e1006038. doi: 10.1371/journal.ppat.1006038. eCollection 2016.

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

Behler-Janbeck F1, Takano T2, Maus R1, Stolper J1, Jonigk D3, Tort Tarrés M1, Fuehner T4, Prasse A4, Welte T4,5, Timmer MS6, Stocker BL6, Nakanishi Y7, Miyamoto T8, Yamasaki S2, Maus UA1,5.

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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.

PMID: 27923071 PMCID: PMC5140071 DOI: 10.1371/journal.ppat.1006038

[PubMed - in process]