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

Themacrophage-inducible C-type lectin Mincle has recently been identified to be a pattern recognition receptor sensing myco-bacterial 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 intrave-nous infection withM. bovis BCG, Mincle-KOmice 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-KOmice rela-tive to the numbers in the spleens of wild-type (WT)mice. The effect of adoptive transfer of definedWT leukocyte subsets gener-ated from bonemarrow 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 sub-sets was then determined. Adoptive transfer experiments revealed that Mincle-expressing splenic cDCs rather thanMincle-ex-pressing macrophages contributed to the reconstitution of attenuated splenic antimycobacterial immune responses in Mincle-KOmice after intravenous challenge with BCG. Collectively, we show that expression of Mincle, particularly by cDCs, contributes to the control of splenicM. bovis BCG infection in mice