Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs

Lanbo Shi, Hugh Salamon, Eliseo Eugenin, Richard Pine, Andrea Cooper, Maria L. Gennaro

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

To elucidate the little-known bioenergetic pathways of host immune cells in tuberculosis, a granulomatous disease caused by the intracellular pathogen Mycobacterium tuberculosis, we characterized infected murine lung tissue by transcriptomic profiling and confocal imaging. Transcriptomic analysis revealed changes of host energy metabolism during the course of infection that are characterized by upregulation of key glycolytic enzymes and transporters for glucose uptake, and downregulation of enzymes participating in the tricarboxylic acid cycle and oxidative phosphorylation. Consistent with elevated glycolysis, we also observed upregulation of a transporter for lactate secretion and a V type H+ -ATPase involved in cytosolic pH homeostasis. Transcription profiling results were corroborated by immunofluorescence microscopy showing increased expression of key glycolytic enzymes in macrophages and T cells in granulomatous lesions. Moreover, we found increased mRNA and protein levels in macrophages and T cells of hypoxia inducible factor 1 alpha (HIF-1α), the regulatory subunit of HIF-1, a master transcriptional regulator. Thus, our findings suggest that immune cells predominantly utilize aerobic glycolysis in response to M. tuberculosis infection. This bioenergetic shift is similar to the Warburg effect, the metabolic signature of cancer cells. Finding immunometabolic changes during M. tuberculosis infection opens the way to new strategies for immunotherapy against tuberculosis.

Original languageEnglish (US)
Article number18176
JournalScientific Reports
Volume5
DOIs
StatePublished - Dec 10 2015
Externally publishedYes

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Mycobacterium tuberculosis
Energy Metabolism
Mycobacterium Infections
Glycolysis
Lung
Alpha Subunit Hypoxia-Inducible Factor 1
Monocarboxylic Acid Transporters
Tuberculosis
Up-Regulation
Enzymes
Infection
Macrophages
Vacuolar Proton-Translocating ATPases
T-Lymphocytes
Hypoxia-Inducible Factor 1
Cell Hypoxia
Proton-Translocating ATPases
Citric Acid Cycle
Facilitative Glucose Transport Proteins
Oxidative Phosphorylation

ASJC Scopus subject areas

  • General

Cite this

Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs. / Shi, Lanbo; Salamon, Hugh; Eugenin, Eliseo; Pine, Richard; Cooper, Andrea; Gennaro, Maria L.

In: Scientific Reports, Vol. 5, 18176, 10.12.2015.

Research output: Contribution to journalArticle

Shi, Lanbo ; Salamon, Hugh ; Eugenin, Eliseo ; Pine, Richard ; Cooper, Andrea ; Gennaro, Maria L. / Infection with Mycobacterium tuberculosis induces the Warburg effect in mouse lungs. In: Scientific Reports. 2015 ; Vol. 5.
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