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Molecular structure of the Mycobacterium tuberculosis virulence factor, mycolic acid, determines the elicited inflammatory pattern

(2011) EUROPEAN JOURNAL OF IMMUNOLOGY. 41(2). p.450-460
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Abstract
Mycolic acids (MAs) occur in the cell wall of Mycobacterium tuberculosis as variable mixtures of different classes and chain lengths. Here, we address the relationship between the structure and its inflammatory function of this virulence factor using single synthetic MA isomers, differing in oxygenation class and cis-versus alpha-methyl-trans proximal cyclopropane orientation. Analysis of bronchoalveolar inflammation, lung histopathology and alveolar macrophage transcription revealed a strong dependence on these meromycolic chemistries of mouse pulmonary inflammation in response to intratracheal treatments with MAs. Whereas alpha-MA was inert, oxygenated methoxy- and keto-MA with cis-cyclopropane stereochemistry elicited solid to mild inflammatory responses respectively. In trans-cyclopropane orientation, methoxy-MA partially lost its inflammatory activity and keto-MA exerted anti-inflammatory alternative activation of alveolar macrophages and counteracted cis-methoxy-MA induced airway inflammation. The differential innate immune activities of MAs demonstrated here, dependent on oxygenation class and cis versus alpha-methyl-trans cyclopropane chemistry, identify a novel means for M. tuberculosis to steer host immune responses during infection.
Keywords
Mycolic acid, Mycobacterium tuberculosis, Alveolar macrophage, FATTY-ACIDS, TUBERCLE-BACILLI, KETOMYCOLIC ACIDS, PULMONARY TUBERCULOSIS, 6'-DIMYCOLATE, TREHALOSE 6, CORD FACTOR, SINGLE ENANTIOMERS, CELL-ENVELOPE LIPIDS, NECROSIS-FACTOR-ALPHA, WALL, Pulmonary inflammation

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Chicago
Vander Beken, Seppe, Juma’a R Al Dulayymi, Thomas Naessens, Gani Koza, Max Maza-Iglesias, Richard Rowles, Cornelia Theunissen, et al. 2011. “Molecular Structure of the Mycobacterium Tuberculosis Virulence Factor, Mycolic Acid, Determines the Elicited Inflammatory Pattern.” European Journal of Immunology 41 (2): 450–460.
APA
Vander Beken, S., Al Dulayymi, J. R., Naessens, T., Koza, G., Maza-Iglesias, M., Rowles, R., Theunissen, C., et al. (2011). Molecular structure of the Mycobacterium tuberculosis virulence factor, mycolic acid, determines the elicited inflammatory pattern. EUROPEAN JOURNAL OF IMMUNOLOGY, 41(2), 450–460.
Vancouver
1.
Vander Beken S, Al Dulayymi JR, Naessens T, Koza G, Maza-Iglesias M, Rowles R, et al. Molecular structure of the Mycobacterium tuberculosis virulence factor, mycolic acid, determines the elicited inflammatory pattern. EUROPEAN JOURNAL OF IMMUNOLOGY. 2011;41(2):450–60.
MLA
Vander Beken, Seppe, Juma’a R Al Dulayymi, Thomas Naessens, et al. “Molecular Structure of the Mycobacterium Tuberculosis Virulence Factor, Mycolic Acid, Determines the Elicited Inflammatory Pattern.” EUROPEAN JOURNAL OF IMMUNOLOGY 41.2 (2011): 450–460. Print.
@article{1176358,
  abstract     = {Mycolic acids (MAs) occur in the cell wall of Mycobacterium tuberculosis as variable mixtures of different classes and chain lengths. Here, we address the relationship between the structure and its inflammatory function of this virulence factor using single synthetic MA isomers, differing in oxygenation class and cis-versus alpha-methyl-trans proximal cyclopropane orientation. Analysis of bronchoalveolar inflammation, lung histopathology and alveolar macrophage transcription revealed a strong dependence on these meromycolic chemistries of mouse pulmonary inflammation in response to intratracheal treatments with MAs. Whereas alpha-MA was inert, oxygenated methoxy- and keto-MA with cis-cyclopropane stereochemistry elicited solid to mild inflammatory responses respectively. In trans-cyclopropane orientation, methoxy-MA partially lost its inflammatory activity and keto-MA exerted anti-inflammatory alternative activation of alveolar macrophages and counteracted cis-methoxy-MA induced airway inflammation. The differential innate immune activities of MAs demonstrated here, dependent on oxygenation class and cis versus alpha-methyl-trans cyclopropane chemistry, identify a novel means for M. tuberculosis to steer host immune responses during infection.},
  author       = {Vander Beken, Seppe and Al Dulayymi, Juma'a R and Naessens, Thomas and Koza, Gani and Maza-Iglesias, Max and Rowles, Richard and Theunissen, Cornelia and De Medts, Jelle and Lanckacker, Ellen and Baird, Mark S and Grooten, Johan},
  issn         = {0014-2980},
  journal      = {EUROPEAN JOURNAL OF IMMUNOLOGY},
  keyword      = {Mycolic acid,Mycobacterium tuberculosis,Alveolar macrophage,FATTY-ACIDS,TUBERCLE-BACILLI,KETOMYCOLIC ACIDS,PULMONARY TUBERCULOSIS,6'-DIMYCOLATE,TREHALOSE 6,CORD FACTOR,SINGLE ENANTIOMERS,CELL-ENVELOPE LIPIDS,NECROSIS-FACTOR-ALPHA,WALL,Pulmonary inflammation},
  language     = {eng},
  number       = {2},
  pages        = {450--460},
  title        = {Molecular structure of the Mycobacterium tuberculosis virulence factor, mycolic acid, determines the elicited inflammatory pattern},
  url          = {http://dx.doi.org/10.1002/eji.201040719},
  volume       = {41},
  year         = {2011},
}

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