IL-6 inhibits IFN-纬 induced autophagy in Mycobacterium tuberculosis H37Rv infected macrophages
- 作者：Rajesh Kumar Dutta ; Mahesh Kathania ; Manoj Raje ; Sekhar Majumdar ; majumdar@imtech.res.in ; sekhar_77054@yahoo.com
- 关键词：Autophagy ; IFN-纬 ; IL-6 ; Mycobacteria
- 刊名：The International Journal of Biochemistry and Cell Biology
- 出版年：2012
- 期刊代码：127_13572725
- 类别：med
- 出版时间：June, 2012
- 卷：44
- 期：6
- 页码：942-954
- 文件大小：2790 K
摘要
The significance of IL-6 production in tuberculosis is yet to be fully elucidated, although it is known for quite some time that IL-6 interferes with IFN-纬 induced signal. In order to know which cellular process induced by IFN-纬 is actually counteracted by IL-6, we studied the role of IL-6 on IFN-纬 induced autophagy formation in virulent Mycobacterium tuberculosis infection in THP-1 cells, since it is well characterized that induction of autophagy by IFN-纬 eliminates intracellular mycobacterium by overcoming the phagosome maturation block imposed by bacilli. We report here that IL-6 inhibits both IFN-纬 and starvation induced autophagy in M. tuberculosis H37Rv infected cells. M. tuberculosis H37Rv infection results in time dependent production of IL-6 in THP-1 cells and neutralization of this endogenous IL-6 by anti-IL-6 antibody significantly enhances the IFN-纬 mediated killing of the intracellular bacteria. IL-6 time dependently lowers Atg12-Atg5 complex and therefore inhibits autophagosome biogenesis rather than autophagolysosome formation. IL-6 also affects IFN-纬 mediated stimulation of mTOR, p-38 and JNK pathways. These results clearly indicate that virulent mycobacteria strategically upregulate IL-6 production to combat innate immunity.