title: Cross-reactive immunity to Mycobacterium tuberculosis DosR regulon-encoded antigens in individuals infected with environmental, nontuberculous mycobacteria.
abstract: Mycobacterium tuberculosis DosR regulon-encoded antigens are highly immunogenic in M. 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 to M. 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 of M. 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 to M. 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 of M. tuberculosis antigens to which cross-reactive immunity is induced by NTM infection/exposure. The high conservation of M. tuberculosis DosR regulon-encoded antigens most likely enables them to induce cross-reactive T-cell responses.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Centre, C5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: May Young
authors.initials: MY
authors.lastname: Lin
authors.forename: T B K
authors.initials: TB
authors.lastname: Reddy
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Arend
authors.forename: Annemieke H
authors.initials: AH
authors.lastname: Friggen
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Krista E
authors.initials: KE
authors.lastname: van Meijgaarden
authors.forename: Marleen J C
authors.initials: MJ
authors.lastname: Verduyn
authors.forename: Gary K
authors.initials: GK
authors.lastname: Schoolnik
authors.forename: Michel R
authors.initials: MR
authors.lastname: Klein
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D003429:Cross Reactions; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009161:Mycobacterium / Q000235:genetics / Q000276:immunology*; D009164:Mycobacterium Infections / Q000235:genetics / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D011494:Protein Kinases / Q000235:genetics / Q000276:immunology*; D018085:Regulon / Q000235:genetics / Q000276:immunology; D014374:Tuberculin Test
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C542863:DosR protein, Mycobacterium tuberculosis; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma; D011494:Protein Kinases