IL-22 Produced by Human NK Cells Inhibits Growth of Mycobacterium tuberculosis by Enhancing Phagolysosomal Fusion
IL-22 Produced by Human NK Cells Inhibits Growth of Mycobacterium tuberculosis by Enhancing Phagolysosomal Fusion
复制标题
DOI：
10.4049/jimmunol.0902587
复制
发表时间：
2009-11-15
影响因子：
4.4
通讯作者：
Vankayalapati, Ramakrishna
中科院分区：
文献类型：
--
作者：
Dhiman, Rohan;Indramohan, Mohanalaxmi;Vankayalapati, Ramakrishna
我们确定了人类NK细胞是否可以通过产生IL-22来促进对结核分枝杆菌的免疫防御。CD 3（-）CD 56（+）NK细胞暴露于自体单核细胞和γ射线照射的M.结核病，这取决于IL-15和IL-23的存在，而不是IL-12或IL-18。IL-15刺激的NK细胞表达的DAP 10 mRNA是对照NK细胞的10.6倍，并且DAP 10 siRNA抑制IL-15介导的NK细胞产生IL-22。IL-15激活的NK细胞产生的可溶性因子抑制M.结核病在巨噬细胞中的作用，并且这种作用被抗IL-22逆转。rIL-22能促进巨噬细胞吞噬溶酶体的融合，抑制巨噬细胞的生长。结核我们的结论是，NK细胞可以有助于对M的免疫防御。通过产生IL-22，IL-22通过增强吞噬溶酶体融合抑制细胞内分枝杆菌生长。IL-15和DAP-10诱导NK细胞响应M.结核免疫学杂志，2009，183：6639-6645.
We determined whether human NK cells could contribute to immune defenses against Mycobacterium tuberculosis through production of IL-22. CD3(-)CD56(+) NK cells produced IL-22 when exposed to autologous monocytes and gamma-irradiated M. tuberculosis, and this depended on the presence of IL-15 and IL-23, but not IL-12 or IL-18. IL-15-stimulated NK cells expressed 10.6 times more DAP10 mRNA compared with control NK cells, and DAP10 siRNA inhibited IL-15-mediated IL-22 production by NK cells. Soluble factors produced by IL-15-activated NK cells inhibited growth of M. tuberculosis in macrophages, and this effect was reversed by anti-IL-22. Addition of rIL-22 to infected macrophages enhanced phagolysosomal fusion and reduced growth of M. tuberculosis. We conclude that NK cells can contribute to immune defenses against M. tuberculosis through production of IL-22, which inhibits intracellular mycobacterial growth by enhancing phagolysosomal fusion. IL-15 and DAP-10 elicit IL-22 production by NK cells in response to M. tuberculosis. The Journal of Immunology, 2009, 183: 6639-6645.