title: Macrophage-inducible C-type lectin Mincle-expressing dendritic cells contribute to control of splenic Mycobacterium bovis BCG infection in mice.
abstract: The macrophage-inducible C-type lectin Mincle has recently been identified to be a pattern recognition receptor sensing mycobacterial infection via recognition of the mycobacterial cell wall component trehalose-6',6-dimycolate (TDM). However, its role in systemic mycobacterial infections has not been examined so far. Mincle-knockout (KO) mice were infected intravenously with Mycobacterium bovis BCG to mimic the systemic spread of mycobacteria under defined experimental conditions. After intravenous infection with M. bovis BCG, Mincle-KO mice responded with significantly higher numbers of mycobacterial CFU in spleen and liver, while reduced granuloma formation was observed only in the spleen. At the same time, reduced Th1 cytokine production and decreased numbers of gamma interferon-producing T cells were observed in the spleens of Mincle-KO mice relative to the numbers in the spleens of wild-type (WT) mice. The effect of adoptive transfer of defined WT leukocyte subsets generated from bone marrow cells of zDC(+/DTR) mice (which bear the human diphtheria toxin receptor [DTR] under the control of the classical dendritic cell-specific zinc finger transcription factor zDC) to specifically deplete Mincle-expressing classical dendritic cells (cDCs) but not macrophages after diphtheria toxin application on the numbers of splenic and hepatic CFU and T cell subsets was then determined. Adoptive transfer experiments revealed that Mincle-expressing splenic cDCs rather than Mincle-expressing macrophages contributed to the reconstitution of attenuated splenic antimycobacterial immune responses in Mincle-KO mice after intravenous challenge with BCG. Collectively, we show that expression of Mincle, particularly by cDCs, contributes to the control of splenic M. bovis BCG infection in mice.
authors.affiliation: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Behler
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: Bohling
authors.affiliation: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Knippenberg
authors.affiliation: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Kirchhof
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Fukuoka, University, Kyushu, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagata
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Izykowski
authors.affiliation: Institute of Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Lavinia
authors.initials: L
authors.lastname: Mägel
authors.affiliation: Clinic for Pneumology, Hannover Medical School, Hannover, Germany German Center for Infectious Diseases DZIF, Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Fukuoka, University, Kyushu, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Department of Experimental Pneumology, Hannover Medical School, Hannover, Germany German Center for Infectious Diseases DZIF, Hannover, Germany Maus.Ulrich@mh-hannover.de.
authors.forename: Ulrich A
authors.initials: UA
authors.lastname: Maus
mesh_terms: D000818:Animals; D058491:Bacterial Load; D027682:Cation Transport Proteins; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D006099:Granuloma / Q000382:microbiology / Q000473:pathology; D037181:Lectins, C-Type / Q000172:deficiency / Q000378:metabolism*; D008099:Liver / Q000382:microbiology; D008565:Membrane Proteins / Q000172:deficiency / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology*; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D027682:Cation Transport Proteins; D016207:Cytokines; D037181:Lectins, C-Type; D008565:Membrane Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1; C113583:Clecsf8 protein, mouse