title: C-type Lectin Mincle Recognizes Glucosyl-diacylglycerol of Streptococcus pneumoniae and Plays a Protective Role in Pneumococcal Pneumonia.
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.
authors.affiliation: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Behler-Janbeck
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Tomotsugu
authors.identifier: http://orcid.org/0000-0002-3905-9355
authors.initials: T
authors.lastname: Takano
authors.affiliation: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Maus
authors.affiliation: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stolper
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
authors.affiliation: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
authors.forename: Meritxell
authors.identifier: http://orcid.org/0000-0002-7523-3664
authors.initials: M
authors.lastname: Tort Tarrés
authors.affiliation: Clinic for Pneumology, Hannover Medical School, Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fuehner
authors.affiliation: Clinic for Pneumology, Hannover Medical School, Hannover, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Prasse
authors.affiliation: Clinic for Pneumology, Hannover Medical School, Hannover, Germany.|German Center for Lung Research, partner site BREATH, Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.affiliation: School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Mattie S M
authors.identifier: http://orcid.org/0000-0001-7884-0729
authors.initials: MS
authors.lastname: Timmer
authors.affiliation: School of Chemical and Physical Sciences, Victoria University of Wellington, Wellington, New Zealand.
authors.forename: Bridget L
authors.initials: BL
authors.lastname: Stocker
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.affiliation: Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Miyamoto
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.|German Center for Lung Research, partner site BREATH, Hannover, Germany.
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Maus
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005434:Flow Cytometry; D006017:Glycolipids / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000378:metabolism
chemical_list: C482593:CLEC4D protein, human; C113583:Clecsf8 protein, mouse; D006017:Glycolipids; D037181:Lectins, C-Type; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C014571:glucosyl diacylglycerol