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

摘要

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 Mycobacterium alvei CR-21T and Mycobacterium brumae CR-270T was studied in the cell lines RAW 264.7 and THP-1, and compared to the ability of cord factor from Mycobacterium tuberculosis 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 M. alvei CR-21T and α in M. brumae CR-270T; in both cases they were di-unsaturated instead of cyclopropanated as found in M. tuberculosis. In RAW 264.7 cells, cord factors from M. alvei CR-21T, M. brumae CR-270T and M. tuberculosis differed in their ability to stimulate IL-6, the higher levels corresponding to the cord factor from M. tuberculosis. In THP-1 cells, a similar overall profile of cytokines was found for M. alvei CR-21T and M. brumae CR-270T, with high proportions of IL-1β and TNF-α, and different from M. tuberculosis, where IL-6 and IL-12p40 prevailed. The data obtained indicate that cord factors from the atypical mycobacteria M. alvei CR-21T and M. brumae CR-270T stimulated the secretion of several pro-inflammatory cytokines, although there were some differences with those of M. tuberculosis 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.