Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Nat Immunol. 2010 Aug;11(8):751-8. doi: 10.1038/ni.1904. Epub 2010 Jul 11.
The fate of infected macrophages has an essential role in protection against Mycobacterium tuberculosis by regulating innate and adaptive immunity. M. tuberculosis exploits cell necrosis to exit from macrophages and spread. In contrast, apoptosis, which is characterized by an intact plasma membrane, is an innate mechanism that results in lower bacterial viability. Virulent M. tuberculosis inhibits apoptosis and promotes necrotic cell death by inhibiting production of prostaglandin E(2). Here we show that by activating the 5-lipoxygenase pathway, M. tuberculosis not only inhibited apoptosis but also prevented cross-presentation of its antigens by dendritic cells, which impeded the initiation of T cell immunity. Our results explain why T cell priming in response to M. tuberculosis is delayed and emphasize the importance of early immunity.
受感染的巨噬细胞的命运在通过调节先天和适应性免疫来抵抗结核分枝杆菌方面起着至关重要的作用。结核分枝杆菌利用细胞坏死从巨噬细胞中逸出并传播。相比之下，凋亡是一种先天机制，其特征是完整的质膜，导致细菌活力降低。毒力结核分枝杆菌通过抑制前列腺素 E2 的产生来抑制凋亡并促进坏死性细胞死亡。在这里，我们表明，结核分枝杆菌通过激活 5-脂氧合酶途径，不仅抑制凋亡，还阻止树突状细胞交叉呈递其抗原，从而阻碍 T 细胞免疫的启动。我们的研究结果解释了为什么针对结核分枝杆菌的 T 细胞启动会延迟，并强调了早期免疫的重要性。
