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.
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 tumornecrosis 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.
Authors: Alessandra Romagnoli; Marilena P Etna; Elena Giacomini; Manuela Pardini; Maria Elena Remoli; Marco Corazzari; Laura Falasca; Delia Goletti; Valérie Gafa; Roxane Simeone; Giovanni Delogu; Mauro Piacentini; Roland Brosch; Gian Maria Fimia; Eliana M Coccia Journal: Autophagy Date: 2012-08-13 Impact factor: 16.016
Authors: Tom H M Ottenhoff; Ranjeeta Hari Dass; Ninghan Yang; Mingzi M Zhang; Hazel E E Wong; Edhyana Sahiratmadja; Chiea Chuen Khor; Bachti Alisjahbana; Reinout van Crevel; Sangkot Marzuki; Mark Seielstad; Esther van de Vosse; Martin L Hibberd Journal: PLoS One Date: 2012-09-21 Impact factor: 3.240