title: Specific T cells restore the autophagic flux inhibited by Mycobacterium tuberculosis in human primary macrophages.
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.
authors.affiliation: Translational Research Unit, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Petruccioli
authors.forename: Alessandra
authors.initials: A
authors.lastname: Romagnoli
authors.forename: Marco
authors.initials: M
authors.lastname: Corazzari
authors.forename: Eliana M
authors.initials: EM
authors.lastname: Coccia
authors.forename: Ornella
authors.initials: O
authors.lastname: Butera
authors.forename: Giovanni
authors.initials: G
authors.lastname: Delogu
authors.forename: Mauro
authors.initials: M
authors.lastname: Piacentini
authors.forename: Enrico
authors.initials: E
authors.lastname: Girardi
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Fimia
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001343:Autophagy / Q000276:immunology*; D015153:Blotting, Western; D002450:Cell Communication; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000382:microbiology*; D018613:Microscopy, Confocal; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000472:pathogenicity; D010588:Phagosomes / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000071456:Sequestosome-1 Protein; D013234:Stem Cells / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma