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 the MA molec-ular
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 stere-ochemistry of its mycolates as well as by altering the oxygenation class of the
meromy-colate functional group.
