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

Abstract

The ability to induce several cytokines relevant to tuberculosis (TNF-a, IL-1b, IL-6, IL-12p40 and IL-23) by cord factor (trehalose dimycolate) from Mycobacterium alvei CR-21T andMycobacterium brumae CR-270 T 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 a and and IL-12p40 prevailed. The data obtained indicate that cord factors from the atypical mycobacteria M. alvei CR-21 T and M. brumae CR-270 T 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.

Sacroiliitis secondary to catheter-related bacteremia due to Mycobacterium abscessus (sensu stricto)

“…However, a secondary bone infection or osteomyelitis due to M. abscessus bacteremia is infrequent and, classically, M. abscessus bacteremia has an indolent course in patients and animal models [12]. In our case, the unusual severity of the disease (sacroiliitis) could have been caused by different factors, such as (i) the presence of a pre-existing sacroiliac joint lesion that could have facilitated the M. abscessus infection; (ii) the infection by a rough strain of M. abscessus with more virulence factors than smooth strains [15-17]; (iii) the lack of treatment after the identification of M. abscessus species in the catheter and blood specimens.…”

The cell envelope glycoconjugates ofMycobacterium tuberculosis

“…TDM also contributes to the protection of Mtb from killing by macrophages, is a potent modulator of the activation of macrophages and increases the resistance of mycobacteria to antibiotics (Silva et al ., 1985; Katti et al ., 2008; Axelrod et al ., 2008; Indrigo et al ., 2002, Indrigo et al ., 2003). The study of defined Mtb knock-out mutants deficient in the modification of mycolic acids with cyclopropane rings and oxygenated functions has provided evidence of the impact of the fine structures of the mycolyl substituents of TDM on the biological activities of this glycolipid (Rao et al ., 2005; Linares et al ., 2012). Only recently have TDM receptors been identified at the surface of macrophages.…”

Genetics of Capsular Polysaccharides and Cell Envelope (Glyco)lipids

“…In fact, TDM seems to be a major contributor to the inflammation seen in mycobacterial infections. TDM contributes to protecting Mtb from killing by macrophages, is a potent modulator of the activation of macrophages, stimulates the formation of lung granulomas and enhances the resistance of mycobacteria to antibiotics [152, 154, 156, 158, 159]. The binding of TDM from Mtb to the C-type lectin Mincle is required for activation of macrophages and granuloma formation [158, 160].…”

“…The binding of TDM from Mtb to the C-type lectin Mincle is required for activation of macrophages and granuloma formation [158, 160]. Importantly, the biological activities of TDM are much dependent on the fine structure of their mycolyl substituents [156, 161]. …”