Comparable studies of immunostimulating activitiesin vitroamongMycobacterium bovisbacillus Calmette-Guérin (BCG) substrains

Abstract

During the serial passage of Mycobacterium bovis bacillus Calmette-Guérin (BCG) in different countries after initial seed distribution from the Pasteur Institute, specific insertions and deletions in the genome among BCG substrains were observed and speculated to result in differences in immunological activities. 'Early-shared strains' of BCG (Russia, Moreau, Japan, Sweden, Birkhaug), distributed by the Pasteur Institute, which conserve three types of mycolate (alpha, methoxy, keto) in cell wall, exhibited stronger activities of induction of nitric oxide, interleukin-1beta (IL-1beta), IL-6, IL-8, IL-12 and tumor necrosis factor (TNF)-alpha, from human epithelial cell line A549, human myelomonocytic cell line THP-1 and mouse bone marrow cells in the presence of interferon-gamma (IFN-gamma) than did 'late-shared strains' of BCG (Danish, Glaxo, Mexico, Tice, Connaught, Montreal, Phipps, Australia, Pasteur). The stronger induction of IL-12 and TNF-alpha in the presence of IFN-gamma was also observed by trehalose 6,6'-dimycolate (TDM) extracted from BCG-Japan than by TDM from BCG-Connaught, which lacks the methoxymycolate residue. These results suggest that 'early-shared strains' are more potent immunostimulating agents than 'late-shared strains', which could be attributed partially to methoxymycolate. Our study provides the basic information for immunological characterization of various BCG strains and may contribute to a re-evaluation of them as a reference strain for vaccination against tuberculosis.

Lipid Phenotype of Two Distinct Subpopulations of Mycobacterium bovis Bacillus Calmette-Guérin Tokyo 172 Substrain

“…For global BCG vaccination policy and practice, it is important to understand the heterogeneity in the morphology and genetics of BCG substrains (4,13). The most common characteristic of acid-fast bacteria is that they are rich in lipids, and this may be reflected in the morphology (14,15).…”

Arabino-mycolates derived from cell-wall skeleton of <i>Mycobacterium bovis</i> BCG as a prominent structure for recognition by host immunity

“…The cell-wall skeleton (CWS) of Mycobacterium bovis BCG (BCG-CWS), a microbial adjuvant, has intensively been investigated for decades, and has consequently been shown to possess promising activity as a cancer immunotherapeutic agent (1)(2)(3)(4). Toll-like receptors (TLRs) have been characterized as pattern-recognition receptors that recognize microbial components (5,6).…”

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

“…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.…”