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

Melanie Harriff, Meghan E. Cansler, Katelynne Gardner Toren, Elizabeth T. Canfield, Stephen Kwak, Marielle Gold, David Lewinsohn

Research output: Contribution to journalArticle

46 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere97515
JournalPLoS One
Volume9
Issue number5
DOIs
StatePublished - May 14 2014

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T-cells
Mycobacterium tuberculosis
Vacuoles
vacuoles
epithelial cells
T-lymphocytes
Epithelial Cells
lungs
T-Lymphocytes
Lung
endosomes
Endosomes
Linings
Bacteria
Alveolar Macrophages
Molecules
Infection Control
Inhalation
breathing
disease control

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Human lung epithelial cells contain Mycobacterium tuberculosis in a late endosomal vacuole and are efficiently recognized by CD8+ T Cells. / Harriff, Melanie; Cansler, Meghan E.; Toren, Katelynne Gardner; Canfield, Elizabeth T.; Kwak, Stephen; Gold, Marielle; Lewinsohn, David.

In: PLoS One, Vol. 9, No. 5, e97515, 14.05.2014.

Research output: Contribution to journalArticle

Harriff, Melanie ; Cansler, Meghan E. ; Toren, Katelynne Gardner ; Canfield, Elizabeth T. ; Kwak, Stephen ; Gold, Marielle ; Lewinsohn, David. / Human lung epithelial cells contain Mycobacterium tuberculosis in a late endosomal vacuole and are efficiently recognized by CD8+ T Cells. In: PLoS One. 2014 ; Vol. 9, No. 5.
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