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

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Vander Beken S., Al Dulayymi J. R., Naessens T., Koza G., Maza-Iglesias M., Rowles R., ...Daha Fazla

EUROPEAN JOURNAL OF IMMUNOLOGY, cilt.41, ss.450-460, 2011 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 41
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1002/eji.201040719
  • Dergi Adı: EUROPEAN JOURNAL OF IMMUNOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.450-460
  • Anahtar Kelimeler: Alveolar macrophage, Mycolic acid, Mycobacterium tuberculosis, Pulmonary inflammation, NECROSIS-FACTOR-ALPHA, CELL-ENVELOPE LIPIDS, SINGLE ENANTIOMERS, CORD FACTOR, TREHALOSE 6,6'-DIMYCOLATE, PULMONARY TUBERCULOSIS, KETOMYCOLIC ACIDS, TUBERCLE-BACILLI, FATTY-ACIDS, WALL
  • Bursa Uludağ Üniversitesi Adresli: Hayır

Özet

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.