TY - JOUR
T1 - Specific T cells restore the autophagic flux inhibited by mycobacterium tuberculosis in human primary macrophages
AU - Petruccioli, Elisa
AU - Romagnoli, Alessandra
AU - Corazzari, Marco
AU - Coccia, Eliana M.
AU - Butera, Ornella
AU - Delogu, Giovanni
AU - Piacentini, Mauro
AU - Girardi, Enrico
AU - Fimia, Gian Maria
AU - Goletti, Delia
PY - 2012/5/1
Y1 - 2012/5/1
N2 - 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.
AB - 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.
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U2 - 10.1093/infdis/jis226
DO - 10.1093/infdis/jis226
M3 - Article
C2 - 22457295
AN - SCOPUS:84861550351
VL - 205
SP - 1425
EP - 1435
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
SN - 0022-1899
IS - 9
ER -