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Infection and Immunity, March 2001, p. 1704-1707, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1704-1707.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Immune Response to Infection with Mycobacterium ulcerans

Travis M. Gooding,1,2 Paul D. R. Johnson,3 Dianne E. Campbell,4 John A. Hayman,5 Elizabeth L. Hartland,1,2 Andrew S. Kemp,4 and Roy M. Robins-Browne1,2,*

Department of Microbiology and Immunology, University of Melbourne,1 and Microbiological Research Unit, Murdoch Children's Research Institute, Parkville,2 Department of Infectious Diseases and Clinical Epidemiology, Monash Medical Centre, Clayton,3 Department of Immunology, Royal Children's Hospital, Parkville,4 and Pathology Department, Box Hill Hospital, Box Hill,5 Victoria, Australia

Received 5 September 2000/Returned for modification 9 November 2000/Accepted 18 December 2000

Mycobacterium ulcerans is 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 to M. ulcerans and M. bovis BCG in patients with M. ulcerans disease 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-gamma ). Humoral immunity was assessed by immunoblotting. PBMC from all subjects showed significantly greater proliferation and IFN-gamma production in response to stimulation with living mycobacteria compared with killed cells. However, PBMC from subjects with past or current M. ulcerans disease showed significantly reduced proliferation and production of IFN-gamma in response to stimulation with live M. ulcerans or M. bovis than 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 with M. ulcerans disease, but no control subject, contained antibodies to M. ulcerans. The results indicate that patients with M. ulcerans infection mount an immune response to M. ulcerans as 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 of M. ulcerans-induced disease.

* Corresponding author. Mailing address: Microbiological Research Unit, Royal Children's Hospital, Parkville, Victoria 3052, Australia. Phone: 61 3 9345 5730. Fax: 61 3 9345 5764. E-mail: rbrowne{at}cryptic.rch.unimelb.edu.au.

Infection and Immunity, March 2001, p. 1704-1707, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1704-1707.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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