University of Texas Health Science Center at Tyler, The Center of Biomedical Research, 11937 US Highway 271, Tyler, TX 75708-3154, USA.
Tuberculosis (Edinb). 2009 Dec;89 Suppl 1:S10-4. doi: 10.1016/S1472-9792(09)70005-8.
Mycobacterium tuberculosis comes in contact with pulmonary surfactant, alveolar macrophages and type II epithelial cells. Alveolar type II epithelial cells secrete pulmonary surfactant, a complex mixture of phospholipids and proteins lining the alveolar surface, while alveolar macrophages are involved in surfactant catabolism. Surfactant proteins SP-A and SP-D modulate phagocytosis of M. tuberculosis by alveolar macrophages. We have reported that mice with decreased surfactant catabolism resulting from GM-CSF deficiency are highly susceptible to acute aerosol infection with 100 cfu of M. tuberculosis. Here, we evaluated the lungs of WT, GM-CSF-deficient, and GM-CSF-corrected mice surviving six months after sub-acute aerosol infection of 5-10 cfu M. tuberculosis. We show that GM-CSF-deficient mice develop intra-bronchial and intra-alveolar tuberculosis lesions with numerous mycobacteria, inflammatory cells, and extracellular proteinaceous material containing surfactant protein B (SP-B). In contrast, WT and GM-CSF-corrected mice develop typical epithelioid granulomas containing lymphocytes, SP-B positive cells, and M. tuberculosis bacilli inside macrophages. Our findings support the concept that whole pulmonary surfactant is an important component of host mycobacterial infection in the distal lung.
结核分枝杆菌与肺表面活性剂、肺泡巨噬细胞和 II 型上皮细胞接触。肺泡 II 型上皮细胞分泌肺表面活性剂，这是一种覆盖肺泡表面的复杂磷脂和蛋白质混合物，而肺泡巨噬细胞则参与表面活性剂的代谢。表面活性剂蛋白 SP-A 和 SP-D 调节肺泡巨噬细胞对结核分枝杆菌的吞噬作用。我们曾报道过，由于 GM-CSF 缺乏导致表面活性剂代谢减少的小鼠，对 100 个 CFU 的结核分枝杆菌急性气溶胶感染高度敏感。在这里，我们评估了 WT、GM-CSF 缺陷和 GM-CSF 纠正的小鼠在亚急性气溶胶感染 5-10 CFU M. tuberculosis 六个月后幸存下来的肺部。我们表明，GM-CSF 缺陷小鼠会发展为支气管内和肺泡内结核病变，其中含有大量分枝杆菌、炎症细胞和含有表面活性剂蛋白 B (SP-B) 的细胞外蛋白质物质。相比之下，WT 和 GM-CSF 纠正的小鼠会发展为典型的上皮样肉芽肿，其中含有淋巴细胞、SP-B 阳性细胞和巨噬细胞内的结核分枝杆菌杆菌。我们的发现支持这样一种观点，即整个肺表面活性剂是宿主肺部远端分枝杆菌感染的重要组成部分。
