Identification and Characterization of the ESAT-6 Homologue of Mycobacterium leprae and T-Cell Cross-Reactivity with Mycobacterium tuberculosis

Author:

Geluk Annemieke1,van Meijgaarden Krista E.1,Franken Kees L. M. C.1,Subronto Yanri W.1,Wieles Brigitte1,Arend Sandra M.12,Sampaio Elizabeth P.3,de Boer Tjitske1,Faber William R.4,Naafs Ben5,Ottenhoff Tom H. M.1

Affiliation:

1. Department of Immunohematology and Blood Transfusion

2. Department of Infectious Diseases, Leiden University Medical Center, Leiden

3. Leprosy Laboratory IOC Fiocruz, Rio de Janeiro, Brazil

4. Department of Dermatology, Amsterdam Medical Center, Amsterdam, The Netherlands

5. Department of Dermatology

Abstract

ABSTRACT In this paper we describe identification and characterization of Mycobacterium leprae ESAT-6 (L-ESAT-6), the homologue of M. tuberculosis ESAT-6 (T-ESAT-6). T-ESAT-6 is expressed by all pathogenic strains belonging to the M. tuberculosis complex but is absent from virtually all other mycobacterial species, and it is a promising antigen for immunodiagnosis of tuberculosis (TB). Therefore, we analyzed whether L-ESAT-6 is a similarly powerful tool for the study of leprosy by examining T-cell responses against L-ESAT-6 in leprosy patients, TB patients, and exposed or nonexposed healthy controls from areas where leprosy and TB are endemic and areas where they are not endemic. L-ESAT-6 was recognized by T cells from leprosy patients, TB patients, individuals who had contact with TB patients, and healthy individuals from an area where TB and leprosy are endemic but not by T cells from individuals who were not exposed to M. tuberculosis and M. leprae . Moreover, leprosy patients who were not responsive to M. leprae failed to respond to L-ESAT-6. A very similar pattern was obtained with T-ESAT-6. These results show that L-ESAT-6 is a potent M. leprae antigen that stimulates T-cell-dependent gamma interferon production in a large proportion of individuals exposed to M. leprae . Moreover, our results suggest that there is significant cross-reactivity between T-ESAT-6 and L-ESAT-6, which has implications for the use of ESAT-6 as tool for diagnosis of leprosy and TB in areas where both diseases are endemic.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

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