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 language | English |
|---|---|
| Article number | e1006038 |
| Journal | PLoS pathogens |
| Volume | 12 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 6 2016 |
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All Science Journal Classification (ASJC) codes
- Parasitology
- Microbiology
- Immunology
- Molecular Biology
- Genetics
- Virology
Cite this
C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia. / Behler-Janbeck, Friederike; Takano, Tomotsugu; Maus, Regina; Stolper, Jennifer; Jonigk, Danny; Tort Tarrés, Meritxell; Fuehner, Thomas; Prasse, Antje; Welte, Tobias; Timmer, Mattie S.M.; Stocker, Bridget L.; Nakanishi, Yoichi; Miyamoto, Tomofumi; Yamasaki, Sho; Maus, Ulrich A.
In: PLoS pathogens, Vol. 12, No. 12, e1006038, 06.12.2016.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia
AU - Behler-Janbeck, Friederike
AU - Takano, Tomotsugu
AU - Maus, Regina
AU - Stolper, Jennifer
AU - Jonigk, Danny
AU - Tort Tarrés, Meritxell
AU - Fuehner, Thomas
AU - Prasse, Antje
AU - Welte, Tobias
AU - Timmer, Mattie S.M.
AU - Stocker, Bridget L.
AU - Nakanishi, Yoichi
AU - Miyamoto, Tomofumi
AU - Yamasaki, Sho
AU - Maus, Ulrich A.
PY - 2016/12/6
Y1 - 2016/12/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85007575283&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85007575283&partnerID=8YFLogxK
U2 - 10.1371/journal.ppat.1006038
DO - 10.1371/journal.ppat.1006038
M3 - Article
C2 - 27923071
AN - SCOPUS:85007575283
VL - 12
JO - PLoS Pathogens
JF - PLoS Pathogens
SN - 1553-7366
IS - 12
M1 - e1006038
ER -