Macrophage-Inducible C-Type Lectin Mincle-Expressing Dendritic Cells Contribute to Control of Splenic Mycobacterium bovis BCG Infection in Mice
Macrophage-Inducible C-Type Lectin Mincle-Expressing Dendritic Cells Contribute to Control of Splenic Mycobacterium bovis BCG Infection in Mice
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DOI：
10.1128/iai.02500-14
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发表时间：
2015-01-01
影响因子：
3.1
通讯作者：
Maus, Ulrich A.
中科院分区：
文献类型：
--
作者：
Behler, Friederike;Maus, Regina;Maus, Ulrich A.
巨噬细胞可诱导的C型凝集素Mincle最近被鉴定为通过识别分枝杆菌细胞壁组分海藻糖-6 '，6-二霉菌酸酯（TDM）来感知分枝杆菌感染的模式识别受体。然而，其在系统性分枝杆菌感染中的作用迄今尚未得到研究。在规定的实验条件下，用牛分枝杆菌BCG静脉内感染Mincle敲除（KO）小鼠，以模拟分枝杆菌的全身传播。静脉感染M.牛BCG，Mincle-KO小鼠在脾和肝中以显著更高数量的分枝杆菌CFU应答，而仅在脾中观察到减少的肉芽肿形成。同时，相对于野生型（WT）小鼠脾脏中的数量，在Mincle-KO小鼠脾脏中观察到Th 1细胞因子产生减少和γ干扰素产生T细胞数量减少。过继转移从zDC（+/DTR）小鼠的骨髓细胞产生的确定的WT白细胞亚群的效果（其在经典树突细胞特异性锌指转录因子zDC的控制下携带人白喉毒素受体[DTR]），以特异性耗尽表达Mincle的经典树突细胞（cDC）而对巨噬细胞则无影响。连续转移实验表明，Mincle表达的脾cDC而不是Mincle表达的巨噬细胞有助于Mincle-KO小鼠在BCG静脉内攻击后重建减弱的脾抗分枝杆菌免疫应答。总的来说，我们表明Mincle的表达，特别是cDC的表达，有助于控制脾M。牛卡介苗感染小鼠。
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.