Immune Response to Infection withMycobacterium ulcerans

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Abstract
Mycobacterium ulceransis a slow-growing, acid-fast bacillus that causes chronic necrotizing skin ulcers known as Buruli ulcers. Previously reported information on immunity to this mycobacterium is limited. We examined immune responses toM. ulceransandM. bovisBCG in patients withM. ulceransdisease and in 20 healthy control subjects (10 tuberculin test positive and 10 tuberculin test negative). Cell-mediated immunity was assessed by stimulating peripheral blood mononuclear cells (PBMC) with whole mycobacteria and then measuring PBMC proliferation and the production of gamma interferon (IFN-γ). Humoral immunity was assessed by immunoblotting. PBMC from all subjects showed significantly greater proliferation and IFN-γ production in response to stimulation with living mycobacteria compared with killed cells. However, PBMC from subjects with past or currentM. ulceransdisease showed significantly reduced proliferation and production of IFN-γ in response to stimulation with liveM. ulceransorM. bovisthan PBMC from healthy, tuberculin test-positive subjects (P< 0.001) and showed results in these assays comparable to those of tuberculin test-negative subjects (P> 0.2). Serum from 9 of 11 patients withM. ulceransdisease, but no control subject, contained antibodies toM. ulcerans. The results indicate that patients withM. ulceransinfection mount an immune response toM. ulceransas evidenced by antibody production, but they demonstrate profound systemic T-cell anergy to mycobacterial antigens. These findings may explain some of the distinct clinical and pathological features ofM. ulcerans-induced disease.