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- Title
Specific T Cells Restore the Autophagic Flux Inhibited by Mycobacterium tuberculosis in Human Primary Macrophages.
- Authors
Petruccioli, Elisa; Romagnoli, Alessandra; Corazzari, Marco; Coccia, Eliana M.; Butera, Ornella; Delogu, Giovanni; Piacentini, Mauro; Girardi, Enrico; Fimia, Gian Maria; Goletti, Delia
- Abstract
Background. Autophagy inhibits survival of intracellular Mycobacterium tuberculosis when induced by rapamycin or interferon c (IFN-c), 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-c and tumor necrosis factor a 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.
- Subjects
T cells; MYCOBACTERIUM tuberculosis; MACROPHAGES; RAPAMYCIN; INTERFERONS; AUTOPHAGY
- Publication
Journal of Infectious Diseases, 2012, Vol 205, Issue 9, p1425
- ISSN
0022-1899
- Publication type
Article
- DOI
10.1093/infdis/jis226