Cutting edge:: Vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin
Cutting edge:: Vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin
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DOI：
10.4049/jimmunol.179.4.2060
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发表时间：
2007-08-15
影响因子：
4.4
通讯作者：
Modlin, Robert L.
中科院分区：
文献类型：
--
作者：
Liu, Philip T.;Stenger, Steffen;Modlin, Robert L.
宿主对胞内病原体的防御依赖于先天性和适应性抗菌效应子途径。单核细胞的TLR 2/1活化导致维生素D依赖性的凯萨林菌素的产生，同时，对细胞内结核分枝杆菌具有抗微生物活性。为了确定维生素D触发的抗微生物活性是否需要凯萨林菌素的诱导，将人单核细胞系THP-1用M.结核病H37 Ra，然后用活性维生素D激素1，25-二羟基维生素D（3）（1，25 D（3））活化。1，25 D3刺激导致对细胞内M.结核病与cathelicidin mRNA和蛋白表达的关系。使用针对凯萨林菌素的特异性小干扰RNA（siRNA），1，25 D（3）诱导的凯萨林菌素mRNA和蛋白表达被有效地敲低，而非特异性siRNA对照几乎没有影响。最后，1，25 D3诱导的抗微生物活性在针对凯萨林菌素的siRNA存在下被完全抑制，反而导致分枝杆菌的细胞内生长增强。这些数据表明，cathelicidin是1，25 D（3）-触发的抗细胞内M.结核
Host defense against intracellular pathogens depends upon innate and adaptive antimicrobial effector pathways. TLR2/1-activation of monocytes leads to the vitamin D-dependent production of cathelicidin and, at the same time, an antimicrobial activity against intracellular Mycobacterium tuberculosis. To determine whether induction of cathelicidin was required for the vitamin D-triggered antimicrobial activity, the human monocytic cell line THP-1 was infected with M. tuberculosis H37Ra and then activated with the active vitamin D hormone 1,25-dihydroxyvitamin D(3) (1,25D(3)). 1,25D3 stimulation resulted in antimicrobial activity against intracellular M. tuberculosis and expression of cathelicidin mRNA and protein. Using small interfering RNA (siRNA) specific for cathelicidin, 1,25D(3)-induced cathelicidin mRNA and protein expressions were efflciently knocked down, whereas a nonspecific siRNA control had little effect. Finally, 1,25D3-induced antimicrobial activity was completely inhibited in the presence of siRNA against cathelicidin, instead leading to enhanced intracellular growth of mycobacteria. These data demonstrate that cathelicidin is required for the 1,25D(3)-triggered antimicrobial activity against intracellular M. tuberculosis.