Reiling Norbert, Hölscher Christoph, Fehrenbach Alexandra, Kröger Svenja, Kirschning Carsten J, Goyert Sanna, Ehlers Stefan
Division of Molecular Infection Biology, Research Center Borstel, Borstel, Germany.
J Immunol. 2002 Oct 1;169(7):3480-4. doi: 10.4049/jimmunol.169.7.3480.
Innate resistance against Mycobacterium tuberculosis is thought to depend critically on engagement of pattern recognition receptors on macrophages. However, the relative contribution of these receptors for containing M. tuberculosis infection has remained unexplored in vivo. To address this issue, we infected mice defective in CD14, TLR2, or TLR4 with M. tuberculosis by aerosol. Following infection with 100 mycobacteria, either mutant strain was as resistant as congenic control mice. Granuloma formation, macrophage activation, and secretion of proinflammatory cytokines in response to low-dose aerosol infection were identical in mutant and control mice. However, high-dose aerosol challenge with 2000 CFU M. tuberculosis revealed TLR2-, but not TLR4-defective mice to be more susceptible than control mice. In conclusion, while TLR2 signaling contributes to innate resistance against M. tuberculosis in borderline situations, its function, and that of CD14 and TLR4, in initiating protective responses against naturally low-dose airborne infection is redundant.
对结核分枝杆菌的固有抗性被认为主要依赖于巨噬细胞上模式识别受体的激活。然而，这些受体在控制结核分枝杆菌感染方面的相对作用在体内尚未得到探索。为了解决这个问题，我们通过气溶胶感染了CD14、TLR2或TLR4缺陷的小鼠。在用100个分枝杆菌感染后，任何一种突变株都与同基因对照小鼠一样具有抗性。在低剂量气溶胶感染后，突变小鼠和对照小鼠的肉芽肿形成、巨噬细胞激活以及促炎细胞因子的分泌是相同的。然而，用2000 CFU结核分枝杆菌进行高剂量气溶胶攻击时，发现TLR2缺陷小鼠比对照小鼠更易感，而TLR4缺陷小鼠则不然。总之，虽然TLR2信号通路在临界情况下有助于对结核分枝杆菌的固有抗性，但其功能以及CD14和TLR4在启动针对自然低剂量空气传播感染的保护性反应中的功能是冗余的。
