Human lung epithelial cells contain Mycobacterium tuberculosis in a late endosomal vacuole and are efficiently recognized by CD8⁺ T cells

PLoS One. 2014 May 14;9(5):e97515. doi: 10.1371/journal.pone.0097515. eCollection 2014.

Abstract

Mycobacterium tuberculosis (Mtb) is transmitted via inhalation of aerosolized particles. While alveolar macrophages are thought to play a central role in the acquisition and control of this infection, Mtb also has ample opportunity to interact with the airway epithelium. In this regard, we have recently shown that the upper airways are enriched with a population of non-classical, MR1-restricted, Mtb-reactive CD8⁺ T cells (MAIT cells). Additionally, we have demonstrated that Mtb-infected epithelial cells lining the upper airways are capable of stimulating IFNγ production by MAIT cells. In this study, we demonstrate that airway epithelial cells efficiently stimulate IFNγ release by MAIT cells as well as HLA-B45 and HLA-E restricted T cell clones. Characterization of the intracellular localization of Mtb in epithelial cells indicates that the vacuole occupied by Mtb in epithelial cells is distinct from DC in that it acquires Rab7 molecules and does not retain markers of early endosomes such as Rab5. The Mtb vacuole is also heterogeneous as there is a varying degree of association with Lamp1 and HLA-I. Although the Mtb vacuole shares markers associated with the late endosome, it does not acidify, and the bacteria are able to replicate within the cell. This work demonstrates that Mtb infected lung epithelial cells are surprisingly efficient at stimulating IFNγ release by CD8⁺ T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / microbiology
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Line
  • Coculture Techniques
  • Endosomes / immunology*
  • Endosomes / microbiology
  • Endosomes / pathology
  • Epithelial Cells / immunology*
  • Epithelial Cells / microbiology
  • Epithelial Cells / pathology
  • Gene Expression
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Lysosome-Associated Membrane Glycoproteins / genetics
  • Lysosome-Associated Membrane Glycoproteins / immunology
  • Mycobacterium tuberculosis / immunology*
  • Primary Cell Culture
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / microbiology
  • Respiratory Mucosa / pathology
  • Vacuoles / immunology*
  • Vacuoles / microbiology
  • Vacuoles / pathology
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / immunology

Substances

  • HLA-B Antigens
  • HLA-B45 antigen
  • HLA-E antigen
  • Histocompatibility Antigens Class I
  • LAMP1 protein, human
  • Lysosome-Associated Membrane Glycoproteins
  • rab7 protein
  • Interferon-gamma
  • rab GTP-Binding Proteins