A novel in vitro human macrophage model to study the persistence of Mycobacterium tuberculosis using vitamin D3 and retinoic acid activated THP-1 macrophages

Jaymie L. Estrella, Celestine Kan-Sutton, Xing Gong, Malini Rajagopalan, Dorothy E. Lewis, Robert L. Hunter, N. Tony Eissa, Chinnaswamy Jagannath

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Mycobacterium tuberculosis (Mtb) replicates within the human macrophages and we investigated the activating effects of retinoic acid (RA) and vitamin D3 (VD) on macrophages in relation to the viability of intracellular Mtb. A combination of these vitamins (RAVD) enhanced the levels of DC-SIGN and mannose receptors on THP-1 macrophages that increased mycobacterial uptake but inhibited the subsequent intracellular growth of Mtb by inducing reactive oxygen species and autophagy. RAVD also enhanced antigen presenting and chemotactic receptors on THPs suggesting an activated phenotype for RAVD activated THPs. RAVD mediated activation was also associated with a marked phenotypic change in Mtb infected THPs that fused with adjacent THPs to form multinucleated giant cells (MNGCs). Typically, MNGCs occurred over 30 days of in vitro culture and contained non-replicating persisting Mtb for more than 60 days in culture. Latent tuberculosis occurs in over a third of mankind and we propose that RAVD mediated induction of persistent Mtb within human macrophages provides a novel model to develop therapeutic approaches and investigate pathogenesis of latency.

Original languageEnglish (US)
JournalFrontiers in Microbiology
Volume2
Issue numberAPR
DOIs
StatePublished - 2011

Keywords

  • DC-SIGN
  • Latent tuberculosis
  • Mannose receptor
  • Mycobacterium
  • THP-1
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

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