Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific

Valentina Guerrini, Brendan Prideaux, Landry Blanc, Natalie Bruiners, Riccardo Arrigucci, Sukhwinder Singh, Hsin Pin Ho-Liang, Hugh Salamon, Pei Yu Chen, Karim Lakehal, Selvakumar Subbian, Paul O’brien, Laura E. Via, Clifton E. Barry, Véronique Dartois, Maria Laura Gennaro

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Foam cells are lipid-laden macrophages that contribute to the inflammation and tissue damage associated with many chronic inflammatory disorders. Although foam cell biogenesis has been extensively studied in atherosclerosis, how these cells form during a chronic infectious disease such as tuberculosis is unknown. Here we report that, unlike the cholesterol-laden cells of atherosclerosis, foam cells in tuberculous lung lesions accumulate triglycerides. Consequently, the biogenesis of foam cells varies with the underlying disease. In vitro mechanistic studies showed that triglyceride accumulation in human macrophages infected with Mycobacterium tuberculosis is mediated by TNF receptor signaling through downstream activation of the caspase cascade and the mammalian target of rapamycin complex 1 (mTORC1). These features are distinct from the known biogenesis of atherogenic foam cells and establish a new paradigm for non-atherogenic foam cell formation. Moreover, they reveal novel targets for disease-specific pharmacological interventions against maladaptive macrophage responses.

Original languageEnglish (US)
Article number1007223
JournalPLoS pathogens
Volume14
Issue number8
DOIs
StatePublished - Aug 1 2018
Externally publishedYes

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ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Guerrini, V., Prideaux, B., Blanc, L., Bruiners, N., Arrigucci, R., Singh, S., Ho-Liang, H. P., Salamon, H., Chen, P. Y., Lakehal, K., Subbian, S., O’brien, P., Via, L. E., Barry, C. E., Dartois, V., & Gennaro, M. L. (2018). Storage lipid studies in tuberculosis reveal that foam cell biogenesis is disease-specific. PLoS pathogens, 14(8), [1007223]. https://doi.org/10.1371/journal.ppat.1007223