Macrophage-inducible C-type lectin Mincle-expressing dendritic cells contribute to control of splenic Mycobacterium bovis BCG infection in mice
| Autor: | Tobias Welte, Gabriele Kirchhof, Regina Maus, Danny Jonigk, Nicole Izykowski, Sarah Knippenberg, Lavinia Mägel, Friederike Behler, Ulrich A. Maus, Jennifer Bohling, Masahiro Nagata, Sho Yamasaki |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Adoptive cell transfer
T cell T-Lymphocytes Immunology Colony Count Microbial Spleen Microbiology Immune system medicine Animals Tuberculosis Lectins C-Type Cation Transport Proteins Diphtheria toxin Mice Knockout Mycobacterium bovis Host Response and Inflammation Granuloma biology Pattern recognition receptor Membrane Proteins Dendritic Cells biology.organism_classification Bacterial Load Mice Inbred C57BL Disease Models Animal Infectious Diseases medicine.anatomical_structure Liver Cytokines Parasitology Bone marrow |
| Zdroj: | Infection and immunity. 83(1) |
| ISSN: | 1098-5522 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|