Delineation of molecular species of a family of diacyltrehaloses from Mycobacterium fortuitum by mass spectrometry

Ariza, Maria A.

doi:10.1016/0378-1097(94)90428-6

Cited by 1 publication

(4 citation statements)

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“…1c). These data confirmed the presence of families of various DAT homologues differing by the number of methylene units and/or by the presence of insaturations in the fatty acyl portions of DATs, as has been previously reported (2,6,18). Additionally, the spectra indicated the presence of homologues containing longer fatty acyl chains in DAT purified from M. tuberculosis.…”

Section: Purification and Chemical Characterization Of Datsupporting

confidence: 89%

“…Although DAT is not shared by mycobacteria closely related to the tubercle bacillus, i.e., M. bovis and M. bovis BCG (34), a few strains of M. fortuitum have proved to synthesize this antigenic molecule (2,18). Moreover, DAT purified from both M. tuberculosis and M. fortuitum reference strains have been shown to be interchangeable in terms of antigenicity (44).…”

Section: Purification and Chemical Characterization Of Datmentioning

confidence: 99%

“…Since it has been shown that the chemical and antigenic features of DAT purified from M. tuberculosis are very similar to those of DAT from a reference strain of M. fortuitum (2,6,18,24,44), the latter strain, which is less pathogenic and has a faster growth rate, was used as a surrogate source of the compound for most of the experiments. This is the first time that the effect of DAT on the activation of T lymphocytes is reported.…”

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confidence: 99%

“…We studied the proliferation of the cells by monitoring [ 3 H]thymidine incorporation and by using flow cytometry analysis of cells stained with 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE), a method that allows tracking of individual cell division (27). Since it has been shown that the chemical and antigenic features of DAT purified from M. tuberculosis are very similar to those of DAT from a reference strain of M. fortuitum (2,6,18,24,44), the latter strain, which is less pathogenic and has a faster growth rate, was used as a surrogate source of the compound for most of the experiments. This is the first time that the effect of DAT on the activation of T lymphocytes is reported.…”

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Mycobacterial Di-O-Acyl-Trehalose Inhibits Mitogen- and Antigen-Induced Proliferation of Murine T Cells In Vitro

Saavedra

Segura

Leyva

et al. 2001

Clin Diagn Lab Immunol

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2,3-Di-O-acyl-trehalose (DAT) is a glycolipid located on the outer layer of the Mycobacterium tuberculosis cell envelope. Due to its noncovalent linkage to the mycobacterial peptidoglycan, DAT could easily interact with host cells located in the focus of infection. The aim of the present work was to study the effects of DAT on the proliferation of murine spleen cells. DAT was purified from reference strains of M. tuberculosis, or M. fortuitum as a surrogate source of the compound, by various chromatography and solvent extraction procedures and then chemically identified. Incubation of mouse spleen cells with DAT inhibited in a dose-dependent manner concanavalin A-stimulated proliferation of the cells. Experiments, including the propidium iodide exclusion test, showed that these effects were not due to death of the cells. Tracking of cell division by labeling with 5,6-carboxyfluorescein diacetate succinimidyl ester revealed that DAT reduces the rounds of cell division. Immunofluorescence with an anti-CD3 monoclonal antibody indicated that T lymphocytes were the population affected in our model. Our experiments also suggest that the extent of the suppressive activity is strongly dependent on the structural composition of the acyl moieties in DATs. Finally, the inhibitory effect was also observed on antigen-induced proliferation of mouse spleen cells specific for Toxoplasma gondii. All of these data suggest that DAT could have a role in the T-cell hyporesponsiveness observed in chronic tuberculosis.Mycobacterium tuberculosis, the infectious agent of tuberculosis, is responsible for more deaths than any other single pathogen. It causes 2 to 3 million deaths annually and accounts for more than 30% of the deaths of human immunodeficiency virus-positive individuals (13). Factors affecting the pathogenesis of tuberculosis are complex and poorly defined; however, it is well established that the major common feature in chronic tuberculosis is the suppression of the T-cell immune response (3). For instance, while immune depression and immune activation are simultaneously present in tuberculosis, more profound defects in the cell-mediated immunity, which is largely responsible for protection, are clearly correlated with more extensive tissue damages (43).M. tuberculosis synthesizes both stimulatory and suppressive components for T cells. In general, it is accepted that hostmycobacterium interactions are mediated primarily by specialized molecules expressed on the mycobacterial cell envelope. The immunosuppressive capability of M. tuberculosis is attributed at least in part to lipoarabinomannan (LAM), a major cell wall-associated lipoglycan (21,28,29). However, the M. tuberculosis cell wall contains many other distinctive and chemically unusual components, with a predominance of lipid molecules (12). According to data obtained from M. tuberculosis and M. bovis BCG strains, lipid molecules from the cell wall of mycobacteria can migrate outside from the phagocytic vacuole (1, 5). As a consequence, glycolipids noncovalently lin...

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Section: Purification and Chemical Characterization Of Datsupporting

confidence: 89%

Section: Purification and Chemical Characterization Of Datmentioning

confidence: 99%

mentioning

confidence: 99%

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