Macrophage-Inducible C-Type Lectin Mincle-Expressing Dendritic Cells Contribute to Control of Splenic Mycobacterium bovis BCG Infection in Mice

Friederike Behler, Regina Maus, Jennifer Bohling, Sarah Knippenberg, Gabriele Kirchhof, Masahiro Nagata, Danny Jonigk, Nicole Izykowski, Lavinia Mägel, Tobias Welte, Sho Yamasaki, Ulrich A. Maus

The macrophage inducible C-type lectin Mincle has recently been identified as pattern recognition receptor sensing mycobacterial infection via recognition of mycobacterial cell wall component trehalose-6',6-dimycolate (TDM). However, its role in systemic mycobacterial infections has not been examined so far. Mincle KO mice were infected intravenously with M. bovis BCG to mimic systemic spread of mycobacteria under defined experimental conditions. After intravenous infection with M. bovis BCG, Mincle KO mice responded with significantly higher mycobacterial CFU in spleen and liver, while reduced granuloma formation was only observed in the spleen. At the same time, reduced TH1 cytokine production and decreased numbers of IFN-γ producing T cells were observed in the spleens of Mincle KO mice relative to WT mice. The effect of adoptive transfer of defined WT leukocyte subsets generated from bone marrow cells of zDC(+/DTR) mice to specifically deplete Mincle-expressing classical dendritic cells (cDC) but not macrophages after diphtheria toxin application on splenic and hepatic CFU and T cell subsets was then determined. Adoptive transfer experiments revealed that Mincle-expressing splenic cDC rather than Mincle-expressing macrophages contributed to reconstitute attenuated splenic antimycobacterial immune responses in Mincle KO mice after intravenous challenge with BCG. Collectively, we show that expression of Mincle particularly by cDC contributes to control splenic M. bovis BCG infection in mice.