Mycobacterial mycolic acids as immunoregulatory lipid antigens in the resistance to tuberculosis

Abstract

Tuberculosis has returned with vengeance mainly due to the resurgence of multi drug resistant strains incurred by non-compliance to the 6-9 months chemotherapy programme. Co-infection with HIV, which disorientates the immune response, has aggravated the situation. This study was built on previous observations that indicated that the major lipid cell wall component of M. tuberculosis, i.e. mycolic acids, a wax that envelopes and protects the bacillus from the hostile host immune system, can be purified and administered to animals for protection against subsequent tuberculosis induction. It was established in this study that mycolic acids pre-treatment can significantly protect mice upon subsequent intranasal infection with M. tuberculosis and that this protection is not attributed so much to the T helper cell immunity, but rather through induction of innate immunity. In the murine AIDS model, innate immunity induced by mycolic acids pre-treatment was not enough to protect the virally immunocompromised mice against subsequent M. tuberculosis infection. Mycolic acids administration in mice did not support tuberculosis chemotherapy to enable shortening of the duration of chemotherapy. In human tuberculosis patients, antibodies to mycolic acids could be measured in a specially adapted configuration of a resonant mirror biosensor. The preliminary investigation opened up the possibility that the prevalence of anti-mycolic acids antibodies in tuberculosis patients may be measured as a surrogate marker for tuberculosis infection. An apparent cross-reactivity between mycolic acids and cholesterol in binding to tuberculosis patient antibodies may provide far reaching insight in the role of the mycolic acids in the cell wall to facilitate infection. This research contributed significantly to the understanding of the host-pathogen interaction in tuberculosis, to open up fresh approaches to improved diagnosis and chemotherapy.