Ryffel Bernhard, Fremond Cecile, Jacobs Muazzam, Parida Shreemanta, Botha Tania, Schnyder Bruno, Quesniaux Valerie
CNRS, IEM2815 Orleans, France.
Tuberculosis (Edinb). 2005 Sep-Nov;85(5-6):395-405. doi: 10.1016/j.tube.2005.08.021. Epub 2005 Oct 27.
Toll-like receptors (TLRs) play a critical role in the recognition of several pathogens, including Mycobacterium tuberculosis. Mycobacterial antigens recognize distinct TLRs resulting in rapid activation of cells of the innate immune system. Ablation of most of the TLR signalling as in mice deficient for the common adaptor protein MyD88 reveals that TLR is crucial for the activation of an innate immune response. MyD88-deficient mice are unable to clear virulent mycobacteria and succumb to acute necrotic pneumonia. Despite the profound defect of the innate immune response, MyD88 deficiency allows the emergence of an adaptive immunity. These data demonstrate that activation of multiple TLRs contributes to an efficient innate response to mycobacteria, while MyD88-dependent signalling is dispensable to generate adaptive immunity.
Toll样受体(TLRs)在识别包括结核分枝杆菌在内的多种病原体中发挥关键作用。分枝杆菌抗原识别不同的TLRs,从而导致天然免疫系统细胞的快速激活。如在缺乏共同衔接蛋白MyD88的小鼠中,大部分TLR信号传导被消除,这表明TLR对于天然免疫反应的激活至关重要。MyD88缺陷小鼠无法清除有毒力的分枝杆菌,并死于急性坏死性肺炎。尽管天然免疫反应存在严重缺陷,但MyD88缺陷仍允许适应性免疫的出现。这些数据表明,多种TLRs的激活有助于对分枝杆菌产生有效的天然反应,而MyD88依赖性信号传导对于产生适应性免疫并非必需。