Open AccessCross-Reactive Immunity to Mycobacterium tuberculosis DosR Regulon-Encoded Antigens in Individuals Infected with Environmental, Nontuberculous Mycobacteria
Author(s) -
Min Lin,
T. B. K. Reddy,
Sandra M. Arend,
Annemieke H. Friggen,
Kees L. M. C. Franken,
Krista E. van Meijgaarden,
Marleen J. C. Verduyn,
Gary K. Schoolnik,
Michèl R. Klein,
Tom H. M. Ottenhoff
Publication year - 2009
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00457-09
Subject(s) - regulon , mycobacterium tuberculosis , tuberculosis , biology , antigen , microbiology and biotechnology , immunology , virology , genetics , medicine , gene , regulation of gene expression , pathology
Mycobacterium tuberculosis DosR regulon-encoded antigens are highly immunogenic inM. tuberculosis -infected humans and are associated with latent tuberculosis infection. We have investigated the hypothesis that infection with or exposure to nontuberculous mycobacteria (NTM) can induce cross-reactive immunity toM. tuberculosis DosR regulon-encoded antigens since responsiveness has been observed in non-M. tuberculosis -exposed but purified protein derivative-responsive individuals.M. tuberculosis DosR regulon-encoded antigen-specific T-cell responses were studied in peripheral blood mononuclear cells (PBMCs) of NTM-infected/exposed individuals. BLASTP was used to determine the presence ofM. tuberculosis DosR regulon-encoded protein orthologs among environmental mycobacteria and nonmycobacteria. Significant gamma interferon production was observed in PBMCs from NTM-infected/exposed individuals in response toM. tuberculosis DosR regulon-encoded antigens. DosR regulon-encoded protein orthologs were prominently present in tuberculous and environmental mycobacteria and surprisingly also in nonmycobacteria. The ubiquitous presence of the highly conserved DosR master regulator protein Rv3133c suggests that this is a general adaptive bacterial response regulator. We report a first series ofM. tuberculosis antigens to which cross-reactive immunity is induced by NTM infection/exposure. The high conservation ofM. tuberculosis DosR regulon-encoded antigens most likely enables them to induce cross-reactive T-cell responses.