Cord factors from atypical mycobacteria (, ) stimulate the secretion of some pro-inflammatory cytokines of relevance in tuberculosis Free

Abstract

The ability to induce several cytokines relevant to tuberculosis (TNF-α, IL-1β, IL-6, IL-12p40 and IL-23) by cord factor (trehalose dimycolate) from CR-21 and CR-270 was studied in the cell lines RAW 264.7 and THP-1, and compared to the ability of cord factor from H37Rv, where this glycolipid appears to be implicated in the pathogenesis of tuberculosis. Details of the fine structure of these molecules were obtained by NMR and MS. The mycoloyl residues were identified as α and (ω-1)-methoxy in CR-21 and α in CR-270; in both cases they were di-unsaturated instead of cyclopropanated as found in . In RAW 264.7 cells, cord factors from CR-21, CR-270 and differed in their ability to stimulate IL-6, the higher levels corresponding to the cord factor from . In THP-1 cells, a similar overall profile of cytokines was found for CR-21 and CR-270, with high proportions of IL-1β and TNF-α, and different from , where IL-6 and IL-12p40 prevailed. The data obtained indicate that cord factors from the atypical mycobacteria CR-21 and CR-270 stimulated the secretion of several pro-inflammatory cytokines, although there were some differences with those of H37Rv. This finding seems to be due to their particular mycoloyl substituents and could be of interest when considering the potential adjuvanticity of these molecules.

Funding
This study was supported by the:
  • Ministerio de Ciencia e Innovación, Spain
  • European Union, FEDER (Award PI080079)
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2012-11-01
2024-03-29
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