{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:46:54Z","timestamp":1791323214378,"version":"4.3.1"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2006,3,10]],"date-time":"2006-03-10T00:00:00Z","timestamp":1141948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004339","name":"Stanley Thomas Johnson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004339","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ghana Government"},{"name":"Amt f\u00fcr Ausbildungsbeitr\u00e4ge of the county Basel-Stadt"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,3,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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-\u03b3 (IFN-\u03b3) 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-\u03b3 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-\u03b3 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-\u03b3 responses was not caused by diminished IL-12 production. Several months after surgical excision of BU lesions, IFN-\u03b3 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.<\/jats:p>","DOI":"10.1189\/jlb.1005581","type":"journal-article","created":{"date-parts":[[2006,3,11]],"date-time":"2006-03-11T02:14:17Z","timestamp":1142043257000},"page":"1150-1156","source":"Crossref","is-referenced-by-count":46,"title":["Systemic suppression of interferon-\u03b3 responses in Buruli ulcer patients resolves after surgical excision of the lesions caused by the extracellular pathogen Mycobacterium ulcerans"],"prefix":"10.1093","volume":"79","author":[{"given":"Dorothy","family":"Yeboah-Manu","sequence":"first","affiliation":[{"name":"Noguchi Memorial Institute for Medical Research, University of Ghana , Legon"},{"name":"Swiss Tropical Institute, Molecular Immunology , Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Peduzzi","sequence":"additional","affiliation":[{"name":"Swiss Tropical Institute, Molecular Immunology , Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernestina","family":"Mensah-Quainoo","sequence":"additional","affiliation":[{"name":"Ghana Health Service , Amasaman, Ga District, Ghana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adwoa","family":"Asante-Poku","sequence":"additional","affiliation":[{"name":"Noguchi Memorial Institute for Medical Research, University of Ghana , Legon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ofori-Adjei","sequence":"additional","affiliation":[{"name":"Noguchi Memorial Institute for Medical Research, University of Ghana , Legon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerd","family":"Pluschke","sequence":"additional","affiliation":[{"name":"Swiss Tropical Institute, Molecular Immunology , Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A","family":"Daubenberger","sequence":"additional","affiliation":[{"name":"Swiss Tropical Institute, Molecular Immunology , Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2006,3,10]]},"reference":[{"key":"2023033015235841300_cit-1","volume-title":"Buruli Ulcer: Diagnosis of Mycobacterium ulcerans Disease","author":"Portaels","year":"2001"},{"key":"2023033015235841300_cit-2","volume-title":"Buruli Ulcer: Mycobacterium ulcerans Infection","author":"Asiedu","year":"2000"},{"key":"2023033015235841300_cit-3","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1371\/journal.pmed.0020108","article-title":"Buruli ulcer (M. ulcerans infection): new insights, new hope for disease control","volume":"2","author":"Johnson","year":"2005","journal-title":"PLoS Med."},{"key":"2023033015235841300_cit-4","volume-title":"Buruli Ulcer: Management of Mycobacterium ulcerans Disease","author":"Buntine","year":"2001"},{"key":"2023033015235841300_cit-5","doi-asserted-by":"crossref","first-page":"594","DOI":"10.3109\/00313028509084759","article-title":"The pathology of Mycobacterium ulcerans infection","volume":"17","author":"Hayman","year":"1985","journal-title":"Pathology"},{"key":"2023033015235841300_cit-6","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1126\/science.283.5403.854","article-title":"Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence","volume":"283","author":"George","year":"1999","journal-title":"Science"},{"key":"2023033015235841300_cit-7","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1128\/IAI.68.2.877-883.2000","article-title":"A Mycobacterium ulcerans toxin, mycolactone, causes apoptosis in guinea pig ulcers and tissue culture cells","volume":"68","author":"George","year":"2000","journal-title":"Infect. Immun."},{"key":"2023033015235841300_cit-8","doi-asserted-by":"crossref","first-page":"7182","DOI":"10.1128\/IAI.69.11.7182-7186.2001","article-title":"Mycobacterium ulcerans cytotoxicity in an adipose cell model","volume":"69","author":"Dobos","year":"2001","journal-title":"Infect. Immun."},{"key":"2023033015235841300_cit-9","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/path.1700880122","article-title":"Mycobacterial skin ulcers in Uganda: histopathological and experimental aspects","volume":"88","author":"Dodge","year":"1964","journal-title":"J. Pathol. Bacteriol."},{"key":"2023033015235841300_cit-10","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1136\/jcp.46.1.5","article-title":"Out of Africa: observations on the histopathology of Mycobacterium ulcerans infection","volume":"46","author":"Hayman","year":"1993","journal-title":"J. Clin. Pathol."},{"key":"2023033015235841300_cit-11","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S1473-3099(04)01203-4","article-title":"Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae","volume":"4","author":"van de Vosse","year":"2004","journal-title":"Lancet Infect. Dis."},{"key":"2023033015235841300_cit-12","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/BF00812260","article-title":"Th1\/Th2 balance in infection","volume":"21","author":"Infante-Duarte","year":"1999","journal-title":"Springer Semin. Immunopathol."},{"key":"2023033015235841300_cit-13","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1146\/annurev.immunol.15.1.749","article-title":"Cellular responses to interferon-\u03b3","volume":"15","author":"Boehm","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"2023033015235841300_cit-14","doi-asserted-by":"crossref","first-page":"5562","DOI":"10.1128\/IAI.70.10.5562-5567.2002","article-title":"Cytokine profiles of patients infected with Mycobacterium ulcerans and unaffected household contacts","volume":"70","author":"Gooding","year":"2002","journal-title":"Infect. Immun."},{"key":"2023033015235841300_cit-15","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1128\/IAI.69.3.1704-1707.2001","article-title":"Immune response to infection with","volume":"69","author":"Gooding","year":"2001","journal-title":"Mycobacterium ulcerans. Infect. Immun."},{"key":"2023033015235841300_cit-16","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1086\/368315","article-title":"Acquired T-helper 1 lymphocyte anergy following infection with","volume":"36","author":"Gooding","year":"2003","journal-title":"Mycobacterium ulcerans. Clin. Infect. Dis."},{"key":"2023033015235841300_cit-17","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1128\/IAI.72.2.958-965.2004","article-title":"Differential production of systemic and intralesional \u03b3 interferon and interleukin-10 in nodular and ulcerative forms of Buruli disease","volume":"72","author":"Prevot","year":"2004","journal-title":"Infect. Immun."},{"key":"2023033015235841300_cit-18","first-page":"125","article-title":"Cytokine responses to stimulation of whole blood from patients with buruli ulcer disease in Ghana","volume":"12","author":"Westenbrink","year":"2005","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"2023033015235841300_cit-19","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1002\/eji.1830270422","article-title":"Comparative analysis of \u03b1 \u03b2 and \u03b3 \u0394 T cell activation by Mycobacterium tuberculosis and isopentenyl pyrophosphate","volume":"27","author":"Wesch","year":"1997","journal-title":"Eur. J. Immunol."},{"key":"2023033015235841300_cit-20","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.vaccine.2003.08.019","article-title":"Influenza virosomes enhance class I restricted CTL induction through CD4+ T cell activation","volume":"22","author":"Schumacher","year":"2004","journal-title":"Vaccine"},{"key":"2023033015235841300_cit-21","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1111\/j.1365-2249.2004.02472.x","article-title":"Recognition of non-peptide antigens by human V \u03b3 9V \u0394 2 T cells requires contact with cells of human origin","volume":"136","author":"Green","year":"2004","journal-title":"Clin. Exp. Immunol."},{"key":"2023033015235841300_cit-22","doi-asserted-by":"crossref","first-page":"5875","DOI":"10.1128\/JCM.42.12.5875-5876.2004","article-title":"Evaluation of decontamination methods and growth media for primary isolation of Mycobacterium ulcerans from surgical specimens","volume":"42","author":"Yeboah-Manu","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"2023033015235841300_cit-23","doi-asserted-by":"crossref","first-page":"520","DOI":"10.4269\/ajtmh.2004.70.520","article-title":"Buruli ulcer disease in Cameroon rediscovered","volume":"70","author":"Noeske","year":"2004","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"2023033015235841300_cit-24","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/S0264-410X(02)00541-8","article-title":"Immunostimulating reconstituted influenza virosomes","volume":"21","author":"Zurbriggen","year":"2003","journal-title":"Vaccine"},{"key":"2023033015235841300_cit-25","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S1046-2023(03)00124-5","article-title":"Quantification and characterization of specific T-cells by antigen-specific cytokine production using ELISPOT assay or intracellular cytokine staining","volume":"31","author":"Letsch","year":"2003","journal-title":"Methods"},{"key":"2023033015235841300_cit-26","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nri1001","article-title":"Interleukin-12 and the regulation of innate resistance and adaptive immunity","volume":"3","author":"Trinchieri","year":"2003","journal-title":"Nat. Rev. Immunol."},{"key":"2023033015235841300_cit-27","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.micinf.2005.03.004","article-title":"Sensing cell stress and transformation through V\u03b39\/V\u03942 T cell-mediated recognition of the isoprenoid pathway metabolites","volume":"7","author":"Bonneville","year":"2005","journal-title":"Microbes Infect."},{"key":"2023033015235841300_cit-28","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1126\/science.1068819","article-title":"Adaptive immune response of V\u03b32V\u03942+ T cells during mycobacterial infections","volume":"295","author":"Shen","year":"2002","journal-title":"Science"},{"key":"2023033015235841300_cit-29","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.4049\/jimmunol.157.9.4222","article-title":"Disease-specific changes in \u03b3\/\u0394 T cell repertoire and function in patients with pulmonary tuberculosis","volume":"157","author":"Li","year":"1996","journal-title":"J. Immunol."},{"key":"2023033015235841300_cit-30","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.4049\/jimmunol.168.3.1484","article-title":"Lack of CD27-CD45RA-V \u03b3 9V \u0394 2+ T cell effectors in immuno-compromised hosts and during active pulmonary tuberculosis","volume":"168","author":"Gioia","year":"2002","journal-title":"J. Immunol."},{"key":"2023033015235841300_cit-31","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/S1472-9792(02)00054-9","article-title":"Human immunity to Mycobacterium tuberculosis: T cell subsets and antigen processing","volume":"83","author":"Boom","year":"2003","journal-title":"Tuberculosis (Edinb.)"},{"key":"2023033015235841300_cit-32","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1086\/345766","article-title":"Selective depression of interferon-\u03b3 and granulysin production with increase of proliferative response by V\u03b39\/V\u03942 T cells in children with tuberculosis","volume":"186","author":"Dieli","year":"2002","journal-title":"J. Infect. Dis."},{"key":"2023033015235841300_cit-33","doi-asserted-by":"crossref","first-page":"3928","DOI":"10.4049\/jimmunol.163.7.3928","article-title":"The inhibitory action of Mycobacterium ulcerans soluble factor on monocyte\/T cell cytokine production and NF-\u03ba B function","volume":"163","author":"Pahlevan","year":"1999","journal-title":"J. Immunol."},{"key":"2023033015235841300_cit-34","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1093\/infdis\/157.3.577","article-title":"Immunosuppressive properties of the soluble toxin from","volume":"157","author":"Pimsler","year":"1988","journal-title":"Mycobacterium ulcerans. J. Infect. Dis."},{"key":"2023033015235841300_cit-35","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0928-8244(03)00166-4","article-title":"Restoration of mycobacterial antigen-induced proliferation and interferon-\u03b3 responses in peripheral blood mononuclear cells of tuberculosis patients upon effective chemotherapy","volume":"38","author":"Al Attiyah","year":"2003","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"2023033015235841300_cit-36","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1046\/j.1365-3083.1999.00492.x","article-title":"In vitro synthesis of interferon-\u03b3, interleukin-4, transforming growth factor-\u03b2 and interleukin-1 \u03b2 by peripheral blood mononuclear cells from tuberculosis patients: relationship with the severity of pulmonary involvement","volume":"49","author":"Dlugovitzky","year":"1999","journal-title":"Scand. J. Immunol."},{"key":"2023033015235841300_cit-37","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1046\/j.1365-2249.2000.01394.x","article-title":"Influence of disease severity on nitrite and cytokine production by peripheral blood mononuclear cells (PBMC) from patients with pulmonary tuberculosis (TB)","volume":"122","author":"Dlugovitzky","year":"2000","journal-title":"Clin. Exp. Immunol."},{"key":"2023033015235841300_cit-38","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1046\/j.1365-2249.2002.01858.x","article-title":"Profiles of IFN-\u03b3 and its regulatory cytokines (IL-12, IL-18 and IL-10) in peripheral blood mononuclear cells from patients with multidrug-resistant tuberculosis","volume":"128","author":"Lee","year":"2002","journal-title":"Clin. Exp. Immunol."},{"key":"2023033015235841300_cit-39","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1097\/00001432-200306000-00004","article-title":"Dynamics of cytokine generation in patients with active pulmonary tuberculosis","volume":"16","author":"Jo","year":"2003","journal-title":"Curr. Opin. Infect. Dis."},{"key":"2023033015235841300_cit-40","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1086\/314852","article-title":"Sequestration of T lymphocytes to body fluids in tuberculosis: reversal of anergy following chemotherapy","volume":"180","author":"Dieli","year":"1999","journal-title":"J. Infect. Dis."},{"key":"2023033015235841300_cit-41","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/nature02837","article-title":"A glycolipid of hyper-virulent tuberculosis strains that inhibits the innate immune response","volume":"431","author":"Reed","year":"2004","journal-title":"Nature"},{"key":"2023033015235841300_cit-42","doi-asserted-by":"crossref","first-page":"5511","DOI":"10.1128\/IAI.72.9.5511-5514.2004","article-title":"Differential monocyte activation underlies strain-specific Mycobacterium tuberculosis pathogenesis","volume":"72","author":"Manca","year":"2004","journal-title":"Infect. Immun."},{"key":"2023033015235841300_cit-43","doi-asserted-by":"crossref","first-page":"9456","DOI":"10.1073\/pnas.91.20.9456","article-title":"Definition of a human suppressor T-cell epitope","volume":"91","author":"Mutis","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023033015235841300_cit-44","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/ni1181","article-title":"Natural regulatory T cells in infectious disease","volume":"6","author":"Belkaid","year":"2005","journal-title":"Nat. Immunol."}],"container-title":["Journal of Leukocyte Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/79\/6\/1150\/49643906\/jlb1150.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jleukbio\/article-pdf\/79\/6\/1150\/49643906\/jlb1150.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,30]],"date-time":"2023-03-30T22:34:03Z","timestamp":1680215643000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jleukbio\/article\/79\/6\/1150\/6922826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3,10]]},"references-count":44,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2006,3,10]]},"published-print":{"date-parts":[[2006,3,10]]}},"URL":"https:\/\/doi.org\/10.1189\/jlb.1005581","relation":{},"ISSN":["1938-3673","0741-5400"],"issn-type":[{"value":"1938-3673","type":"electronic"},{"value":"0741-5400","type":"print"}],"subject":[],"published-other":{"date-parts":[[2006,6]]},"published":{"date-parts":[[2006,3,10]]}}}