Specific T cells restore the autophagic flux inhibited by mycobacterium tuberculosis in human primary macrophages

Elisa Petruccioli, Alessandra Romagnoli, Marco Corazzari, Eliana M. Coccia, Ornella Butera, Giovanni Delogu, Mauro Piacentini, Enrico Girardi, Gian Maria Fimia, Delia Goletti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1425-1435
Number of pages11
JournalJournal of Infectious Diseases
Volume205
Issue number9
DOIs
Publication statusPublished - May 1 2012

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

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