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

Muriel Smet, Charlotte Pollard, Ans De Beuckelaer, Lien Van Hoecke, Seppe Vander Beken, Stefaan De Koker, Juma'a R. Al-Dulayymi, Kris Huygen, Jan Verschoor, Mark Baird, Johan Grooten

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Mycolic acids (MAs) are highly hydrophobic long-chain α-alkyl β-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 theMA 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.
    Original languageEnglish
    Pages (from-to)2149-2154
    Number of pages6
    JournalEuropean Journal of Immunology
    Volume46
    Early online date29 Jul 2016
    DOIs
    Publication statusPublished - 7 Sept 2016

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