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

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

Author information

1
Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
2
Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
3
Institute of Pathology, Hannover Medical School, Hannover, Germany.
4
Clinic for Pneumology, Hannover Medical School, Hannover, Germany.
5
German Center for Lung Research, partner site BREATH, Hannover, Germany.
6
School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington, New Zealand.
7
Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
8
Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

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
[Indexed for MEDLINE]
Free PMC Article

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