TY - JOUR

T1 - Mycobacterium tuberculosis-associated synthetic mycolates differentially exert immune stimulatory adjuvant activity

AU - Smet, Muriel

AU - Pollard, Charlotte

AU - De Beuckelaer, Ans

AU - Van Hoecke, Lien

AU - Beken, Seppe Vander

AU - De Koker, Stefaan

AU - Al-Dulayymi, Juma'a R.

AU - Huygen, Kris

AU - Verschoor, Jan

AU - Baird, Mark

AU - Grooten, Johan

PY - 2016/9/7

Y1 - 2016/9/7

N2 - 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 immunestimulatory 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 stereochemistryof its mycolates as well as by altering the oxygenation class of the meromycolatefunctional group.

AB - 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 immunestimulatory 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 stereochemistryof its mycolates as well as by altering the oxygenation class of the meromycolatefunctional group.

U2 - 10.1002/eji.201646357

DO - 10.1002/eji.201646357

M3 - Article

VL - 46

SP - 2149

EP - 2154

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 1521-4141

ER -