Systemic suppression of interferon-gamma responses in Buruli ulcer patients resolves after surgical excision of the lesions caused by the extracellular pathogen Mycobacterium ulcerans.
Buruli ulcer (BU), caused by Mycobacterium ulcerans, is the third most common mycobacterial infection in immunocompetent humans besides tuberculosis and leprosy. We have compared by ex vivo enzyme-linked immunospot analysis interferon-gamma (IFN-gamma) responses in peripheral blood mononuclear cells (PBMC) from BU patients, household contacts, and individuals living in an adjacent M. ulcerans nonendemic region. PBMC were stimulated with purified protein derivative (PPD) and nonmycobacterial antigens such as reconstituted influenza virus particles and isopentenyl-pyrophosphate. With all three antigens, the number of IFN-gamma spot-forming units was reduced significantly in BU patients compared with the controls from a nonendemic area. This demonstrates for the first time that M. ulcerans infection-associated systemic reduction in IFN-gamma responses is not confined to stimulation with live or dead mycobacteria and their products but extends to other antigens. Interleukin (IL)-12 secretion by PPD-stimulated PBMC was not reduced in BU patients, indicating that reduction in IFN-gamma responses was not caused by diminished IL-12 production. Several months after surgical excision of BU lesions, IFN-gamma responses of BU patients against all antigens used for stimulation recovered significantly, indicating that the measured systemic immunosuppression was not the consequence of a genetic defect in T cell function predisposing for BU but is rather related to the presence of M. ulcerans bacteria.
Noguchi Memorial Institute for Medical Research, University of Ghana, Legon.
Dorothy
D
Yeboah-Manu
Elisabetta
E
Peduzzi
Ernestina
E
Mensah-Quainoo
Adwoa
A
Asante-Poku
David
D
Ofori-Adjei
Gerd
G
Pluschke
Claudia A
CA
Daubenberger
D000293:Adolescent; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000494:pharmacology; D001500:BCG Vaccine; D001427:Bacterial Toxins / Q000378:metabolism; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005192:Family Health; D005260:Female; D005869:Ghana; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007371:Interferon-gamma / Q000172:deficiency / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D018942:Macrolides / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009165:Mycobacterium Infections, Nontuberculous / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D019911:Mycobacterium ulcerans / Q000502:physiology*; D011184:Postoperative Period; D012883:Skin Ulcer / Q000276:immunology / Q000503:physiopathology / Q000601:surgery*; D014373:Tuberculin / Q000494:pharmacology; D014611:Vaccination / Q000706:statistics & numerical data
D000956:Antigens, Viral; D001500:BCG Vaccine; D001427:Bacterial Toxins; D018942:Macrolides; D014373:Tuberculin; D018664:Interleukin-12; D007371:Interferon-gamma