Specific T Cells Restore the Autophagic Flux Inhibited by Mycobacterium tuberculosis in Human Primary Macrophages
Journal of Infectious Diseases, 2012•academic.oup.com
Background. Autophagy inhibits survival of intracellular Mycobacterium tuberculosis when
induced by rapamycin or interferon γ (IFN-γ), but it remains unclear whether M. tuberculosis
itself can induce autophagy and whether T cells play a role in M. tuberculosis–mediated
autophagy. The aim of this study was to evaluate the impact of M. tuberculosis on autophagy
in human primary macrophages and the role of specific T cells in this process. Methods. M.
tuberculosis (H37Rv)–infected macrophages were incubated with naive or M. tuberculosis …
induced by rapamycin or interferon γ (IFN-γ), but it remains unclear whether M. tuberculosis
itself can induce autophagy and whether T cells play a role in M. tuberculosis–mediated
autophagy. The aim of this study was to evaluate the impact of M. tuberculosis on autophagy
in human primary macrophages and the role of specific T cells in this process. Methods. M.
tuberculosis (H37Rv)–infected macrophages were incubated with naive or M. tuberculosis …
Abstract
Background. Autophagy inhibits survival of intracellular Mycobacterium tuberculosis when induced by rapamycin or interferon γ (IFN-γ), but it remains unclear whether M. tuberculosis itself can induce autophagy and whether T cells play a role in M. tuberculosis–mediated autophagy. The aim of this study was to evaluate the impact of M. tuberculosis on autophagy in human primary macrophages and the role of specific T cells in this process.
Methods. M. tuberculosis (H37Rv)–infected macrophages were incubated with naive or M. tuberculosis–specific T cells. Autophagy was evaluated at 4 hours and 8 hours after infection by analyzing the levels of LC3-II (a hallmark of autophagy) and p62 (a protein degraded by autophagy). M. tuberculosis survival was evaluated by counting the colony-forming units.
Results. M. tuberculosis infection of macrophages inhibited the autophagic process at 8 hours after infection. Naive T cells could not rescue this block, whereas M. tuberculosis–specific T cells restored autophagy degradation, accompanied by enhanced bacterial killing. Notably, the effect of M. tuberculosis–specific T cells was not affected by neutralization of endogenous IFN-γ and tumor necrosis factor α and was blocked by preventing contact between macrophages and T cells, suggesting that cell-cell interaction is crucial.
Conclusions. M. tuberculosis inhibits autophagy in human primary macrophages, and specific T cells can restore functional autophagic flux through cell-cell contact.
Oxford University Press