Immune response to infection with Mycobacterium ulcerans

Mycobacterium ulcerans is a slow-growing, acid-fast bacillus that causes ch ronic necrotizing skin ulcers known as Buruli ulcers. Previously reported i nformation on immunity to this mycobacterium is limited. We examined immune responses to M. ulcerans and M. bovis BCG in patients with M. ulcerans dis ease and in 20 healthy control subjects (10 tuberculin test positive and 10 tuberculin test negative). Cell-mediated immunity was assessed by stimulat ing peripheral blood mononuclear cells (PBMC) with whole mycobacteria and t hen measuring PBMC proliferation and the production of gamma interferon (IF N-gamma). Humoral immunity was assessed by immunoblotting. PBMC from all su bjects showed significantly greater proliferation and IFN-gamma production in response to stimulation with living mycobacteria compared with killed ce lls. However, PBMC from subjects with past or current M. ulcerans disease s howed significantly reduced proliferation and production of IFN-gamma in re sponse to stimulation,vith live M. ulcerans or M. bovis than PBMC from heal thy, tuberculin test-positive subjects (P < 0.001) and showed results in th ese assays comparable to those of tuberculin test-negative subjects (P > 0. 2). Serum from 9 of 11 patients with M. ulcerans disease, but no control su bject, contained antibodies to M. ulcerans. The results indicate that patie nts with M. ulcerans infection mount an immune response to M. ulcerans as e videnced by antibody production, but they demonstrate profound systemic T-c ell anergy to mycobacterial antigens. These findings may explain some of th e distinct clinical and pathological features of M. ulcerans-induced diseas e.