A role for tumour necrosis factor-α, complement C5 and interleukin-6 in the initiation and development of the mycobacterial cord factor trehalose 6,6′-dimycolate induced granulomatous response

Abstract

A role for tumour necrosis factor-a, complement C5 and interleukin-6 in the initiation and development of the mycobacterial cord factor trehalose 6,69-dimycolate induced granulomatous response

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

“…Additionaly, its purity was confirmed by two-dimensional TLC as described above for the cord factors from M. alvei and M. brumae. This commercial glycolipid has been used by several authors (Indrigo et al, 2003;Welsh et al, 2008), and similar results to those of the cord factor purified in the laboratory of the authors have been obtained by Dao et al (2008). ) in deuterochloroform/deuteromethanol (6 : 1, v/v).…”

“…Briefly, IL-12p40 favours the Th1 response and the resistance to mycobacterial infections (Cooper & Khader, 2008), but the role of IL-6 is controversial. In some experiments, IL-6 appeared as a pathological cytokine, helping to maintain the granuloma (Welsh et al, 2008), and in others it participated in the differentiation of Th17 cells (cited by Méndez-Samperio, 2010), a subset of T cells that secrete IL-17. TNF-a is, among other functions, critical for the initiation of the granuloma (Russell, 2007), and IL-1b has a role in both innate and adaptative immunity (Korbel et al, 2008).…”

“…It has been demonstrated that cord factor is secreted, together with other lipids, by macrophages infected with Mycobacterium bovis BCG (Rhoades et al, 2003) and that it is the most active lipid from a biological point of view (Geisel et al, 2005). Cord factor induces the secretion of several cytokines, both in vitro and in vivo (Hayashi et al, 2009;Indrigo et al, 2002Indrigo et al, , 2003Lima et al, 2001;Welsh et al, 2008), and that of M. tuberculosis has been employed as an adjuvant in Abbreviations: ESI-TRAP-MS, electrospray ionization-ion trap-MS; 1 H-1 experimental assays of subunit vaccines against tuberculosis (Khader et al, 2007;Lima et al, 2003). In M. tuberculosis, the immuno-modulatory activity of this glycolipid has been shown to rely on the presence of cyclopropane rings and keto and methoxy groups in its mycoloyl substituents (Dao et al, 2008;Rao et al, 2005Rao et al, , 2006.…”

The Role of Tocilizumab in the Treatment of Rheumatoid Arthritis

“…The TNF -/-mice or the IL-6 -/-mice demonstrated that TNF is critical for initiation of the granulomatous response, and IL-6 plays a key role in the granuloma maintenance response (Welsh et al, 2008). Unlike Il-6 -/-mice, TCZ does not completely inactivate the IL-6 system because TCZ works as a competitive inhibitor of IL-6.…”

Virulence Factors and Pathogenicity of Mycobacterium

“…Microspheres coated with TDM showed an increased expression of enzymes and matrix metalloproteinases; molecules associated with tissue remodeling and tissue destruction during caseating granulomas [31]. The inflammatory profile induced by TDM has been related with granuloma development and maintenance, this phenomenon is related with TDM, and is dependent of TNF-α and IL6 expression; also C5a complement factor has been described as part of the granuloma maintenance microenvironment molecule [32].…”