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.