Dhiman Rohan, Indramohan Mohanalaxmi, Barnes Peter F, Nayak Ramesh C, Paidipally Padmaja, Rao L Vijaya Mohan, Vankayalapati Ramakrishna
Center for Pulmonary and Infectious Disease Control, Department of Microbiology and Immunology, University of Texas Health Center, Tyler, TX 75708-3154, USA.
J Immunol. 2009 Nov 15;183(10):6639-45. doi: 10.4049/jimmunol.0902587. Epub 2009 Oct 28.
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.
我们确定了人类自然杀伤细胞（NK细胞）是否能够通过产生白细胞介素-22（IL-22）来参与针对结核分枝杆菌的免疫防御。当暴露于自体单核细胞和经γ射线照射的结核分枝杆菌时，CD3(-)CD56(+) NK细胞会产生IL-22，这取决于IL-15和IL-23的存在，而不依赖于IL-12或IL-18。与对照NK细胞相比，IL-15刺激的NK细胞表达的DAP10 mRNA多10.6倍，并且DAP10小干扰RNA（siRNA）抑制了NK细胞由IL-15介导的IL-22产生。IL-15激活的NK细胞产生的可溶性因子抑制了巨噬细胞中结核分枝杆菌的生长，并且这种作用被抗IL-22所逆转。向受感染的巨噬细胞中添加重组IL-22（rIL-22）增强了吞噬溶酶体融合并减少了结核分枝杆菌的生长。我们得出结论，NK细胞可以通过产生IL-22来参与针对结核分枝杆菌的免疫防御，IL-22通过增强吞噬溶酶体融合来抑制细胞内分枝杆菌的生长。IL-15和DAP-10促使NK细胞响应结核分枝杆菌产生IL-22。
