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Mycobacterium tuberculosis-associated synthetic mycolates differentially exert immune stimulatory adjuvant activity

(2016) EUROPEAN JOURNAL OF IMMUNOLOGY. 46(9). p.2149-2154
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Abstract
Mycolic acids (MAs) are highly hydrophobic long-chain -alkyl -hydroxy fatty acids present in the cell wall of Mycobacterium tuberculosis (Mtb) as a complex mixture of molecules with a common general structure but with variable functional groups in the meromycolate chain. In this study, we addressed the relationship between the MA molecular structure and their contribution to the development of T-cell immune responses. Hereto, we used the model antigen ovalbumin and single synthetic MAs, differing in oxygenation class and cis versus trans proximal cyclopropane configuration, as immune stimulatory agents. Subcutaneous delivery of liposome-formulated MAs with a proximal cis cyclopropane elicited antigen-specific Th1 and cytotoxic T-cell immune responses, whereas intratracheal immunization elicited pulmonary Th17 responses. These immune stimulatory activities depended not only on the cis versus trans proximal cyclopropane configuration but also on the MA oxygenation class. Our study thus shows that both the presence and nature of the functional groups in the meromycolate chain affect the immune stimulatory adjuvant activity of Mtb mycolates and suggests that Mtb bacilli may impact on the host protective immune response by modulating the cis versus trans stereochemistry of its mycolates as well as by altering the oxygenation class of the meromycolate functional group.
Keywords
RESPONSES, INNATE, MYCOLIC ACID, SINGLE ENANTIOMERS, T-cell responses, VACCINES, Mycolic acid, Mycobacterium tuberculosis, Adjuvant biolipids

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MLA
Smet, Muriel et al. “Mycobacterium Tuberculosis-associated Synthetic Mycolates Differentially Exert Immune Stimulatory Adjuvant Activity.” EUROPEAN JOURNAL OF IMMUNOLOGY 46.9 (2016): 2149–2154. Print.
APA
Smet, Muriel, Pollard, C., De Beuckelaer, A., Van Hoecke, L., Vander Beken, S., De Koker, S., Al Dulayymi, J. R., et al. (2016). Mycobacterium tuberculosis-associated synthetic mycolates differentially exert immune stimulatory adjuvant activity. EUROPEAN JOURNAL OF IMMUNOLOGY, 46(9), 2149–2154.
Chicago author-date
Smet, Muriel, Charlotte Pollard, Ans De Beuckelaer, Lien Van Hoecke, Seppe Vander Beken, Stefaan De Koker, Juma’a R Al Dulayymi, et al. 2016. “Mycobacterium Tuberculosis-associated Synthetic Mycolates Differentially Exert Immune Stimulatory Adjuvant Activity.” European Journal of Immunology 46 (9): 2149–2154.
Chicago author-date (all authors)
Smet, Muriel, Charlotte Pollard, Ans De Beuckelaer, Lien Van Hoecke, Seppe Vander Beken, Stefaan De Koker, Juma’a R Al Dulayymi, Kris Huygen, Jan Verschoor, Mark S Baird, and Johan Grooten. 2016. “Mycobacterium Tuberculosis-associated Synthetic Mycolates Differentially Exert Immune Stimulatory Adjuvant Activity.” European Journal of Immunology 46 (9): 2149–2154.
Vancouver
1.
Smet M, Pollard C, De Beuckelaer A, Van Hoecke L, Vander Beken S, De Koker S, et al. Mycobacterium tuberculosis-associated synthetic mycolates differentially exert immune stimulatory adjuvant activity. EUROPEAN JOURNAL OF IMMUNOLOGY. 2016;46(9):2149–54.
IEEE
[1]
M. Smet et al., “Mycobacterium tuberculosis-associated synthetic mycolates differentially exert immune stimulatory adjuvant activity,” EUROPEAN JOURNAL OF IMMUNOLOGY, vol. 46, no. 9, pp. 2149–2154, 2016.
@article{8132678,
  abstract     = {Mycolic acids (MAs) are highly hydrophobic long-chain -alkyl -hydroxy fatty acids present in the cell wall of Mycobacterium tuberculosis (Mtb) as a complex mixture of molecules with a common general structure but with variable functional groups in the meromycolate chain. In this study, we addressed the relationship between the MA molecular structure and their contribution to the development of T-cell immune responses. Hereto, we used the model antigen ovalbumin and single synthetic MAs, differing in oxygenation class and cis versus trans proximal cyclopropane configuration, as immune stimulatory agents. Subcutaneous delivery of liposome-formulated MAs with a proximal cis cyclopropane elicited antigen-specific Th1 and cytotoxic T-cell immune responses, whereas intratracheal immunization elicited pulmonary Th17 responses. These immune stimulatory activities depended not only on the cis versus trans proximal cyclopropane configuration but also on the MA oxygenation class. Our study thus shows that both the presence and nature of the functional groups in the meromycolate chain affect the immune stimulatory adjuvant activity of Mtb mycolates and suggests that Mtb bacilli may impact on the host protective immune response by modulating the cis versus trans stereochemistry of its mycolates as well as by altering the oxygenation class of the meromycolate functional group.},
  author       = {Smet, Muriel and Pollard, Charlotte and De Beuckelaer, Ans and Van Hoecke, Lien and Vander Beken, Seppe and De Koker, Stefaan and Al Dulayymi, Juma'a R and Huygen, Kris and Verschoor, Jan and Baird, Mark S and Grooten, Johan},
  issn         = {0014-2980},
  journal      = {EUROPEAN JOURNAL OF IMMUNOLOGY},
  keywords     = {RESPONSES,INNATE,MYCOLIC ACID,SINGLE ENANTIOMERS,T-cell responses,VACCINES,Mycolic acid,Mycobacterium tuberculosis,Adjuvant biolipids},
  language     = {eng},
  number       = {9},
  pages        = {2149--2154},
  title        = {Mycobacterium tuberculosis-associated synthetic mycolates differentially exert immune stimulatory adjuvant activity},
  url          = {http://dx.doi.org/10.1002/eji.201646357},
  volume       = {46},
  year         = {2016},
}

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