Inflammatory power and adjuvant potential of synthetic glycolipids homologous to mycolate esters of Mycobacterium tuberculosis

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) infection and remains a major global cause of morbidity and mortality. The cell wall of mycobacteria is characterized by long chain fatty acid called mycolic acids (MAs), which are found free or esterified to different sugars. In Mtb, the main classes of MAs present are alpha-, methoxy- and keto-MAs and they differ in their ability to induce lung inflammation. Studies using Mtb strains mutated in the synthesis pathways of MAs have shown that the class of MA bound to trehalose influences its inflammatory power. But the cell wall of Mtb contains variable mixture of MAs and mycolates with different chain lengths. The contribution of all these different classes of mycolates to the inflammatory power of Mtb and their interaction with the different pattern recognition receptors is not clear. In this study, we address the relationship between the structure of the mycolate esters and the inflammatory power in vitro using synthetic mycolates.