An Accord of Nuclear Receptor Expression in M. tuberculosis Infected Macrophages and Dendritic Cells

Sci Rep. 2018 Feb 2;8(1):2296. doi: 10.1038/s41598-018-20769-4.

Abstract

Mycobacterium tuberculosis instigates interactions with host factors to promote its survival within the host inimical conditions. Among such factors, nuclear receptors (NRs) seem to be promising candidates owing to their role in bacterial pathogenesis. However, only few members of NR superfamily have been implicated in M. tuberculosis infection and there is a dearth of comprehensive knowledge about expression or function of the entire superfamily. In this study, we performed detailed expression analysis and identified key NRs getting differentially regulated in murine macrophages and dendritic cells (DC) upon infection with H37Rv. The murine macrophages and DCs infected with H37Rv entailed overlapping changes in the expression of certain NRs which reflect upon the possibility that both cells might utilize similar transcriptional programs upon M. tuberculosis infection. We identified Nr4a3 and Rora, which have not been implicated in M. tuberculosis pathogenesis, undergo similar changes in expression in macrophages and DCs upon H37Rv infection. Interestingly, a similar pattern in their expression was also observed in infected human monocyte derived macrophages and the findings corroborated well with PBMCs obtained from TB patients. This all-inclusive analysis provides the basis for a precise approach in identifying NRs that can be targeted therapeutically in intracellular bacterial infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendritic Cells / microbiology*
  • Gene Expression Profiling
  • Humans
  • Macrophages / microbiology*
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / growth & development*
  • Receptors, Cytoplasmic and Nuclear / analysis*
  • Receptors, Cytoplasmic and Nuclear / genetics

Substances

  • Receptors, Cytoplasmic and Nuclear