Utilize este identificador para referenciar este registo: http://hdl.handle.net/1822/21410

TítuloCellular immunity confers transient protection in experimental buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination
Autor(es)Fraga, Alexandra G.
Martins, Teresa G.
Torrado, Egídio
Huygen, Kris
Portaels, Françoise
Silva, Manuel T.
Castro, António G.
Pedrosa, Jorge
Palavras-chaveBuruli ulcer
Mycobacterium ulcerans
Cell-mediated immune response
Th1 response
DataMar-2012
EditoraPublic Library of Science
RevistaPLoS ONE
Resumo(s)BACKGROUND: Buruli ulcer (BU) is an emerging infectious disease caused by Mycobacterium ulcerans that can result in extensive necrotizing cutaneous lesions due to the cytotoxic exotoxin mycolactone. There is no specific vaccine against BU but reports show some degree of cross-reactive protection conferred by M. bovis BCG immunization. Alternatively, an M. ulcerans-specific immunization could be a better preventive strategy. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the mouse model to characterize the histological and cytokine profiles triggered by vaccination with either BCG or mycolactone-negative M. ulcerans, followed by footpad infection with virulent M. ulcerans. We observed that BCG vaccination significantly delayed the onset of M. ulcerans growth and footpad swelling through the induction of an earlier and sustained IFN-γ T cell response in the draining lymph node (DLN). BCG vaccination also resulted in cell-mediated immunity (CMI) in M. ulcerans-infected footpads, given the predominance of a chronic mononuclear infiltrate positive for iNOS, as well as increased and sustained levels of IFN-γ and TNF. No significant IL-4, IL-17 or IL-10 responses were detected in the footpad or the DLN, in either infected or vaccinated mice. Despite this protective Th1 response, BCG vaccination did not avoid the later progression of M. ulcerans infection, regardless of challenge dose. Immunization with mycolactone-deficient M. ulcerans also significantly delayed the progression of footpad infection, swelling and ulceration, but ultimately M. ulcerans pathogenic mechanisms prevailed. CONCLUSIONS/SIGNIFICANCE: The delay in the emergence of pathology observed in vaccinated mice emphasizes the relevance of protective Th1 recall responses against M. ulcerans. In future studies it will be important to determine how the transient CMI induced by vaccination is compromised.
Tipoarticle
DescriçãoThe authors would like to thank Luís Martins and Miguel Carneiro for laboratory assistance. Author Contributions Conceived and designed the experiments: AGF AGC JP. Performed the experiments: AGF TGM ET. Analyzed the data: AGF. Contributed reagents/materials/analysis tools: FP. Wrote the paper: AGF KH FP MTS AGC JP.
URIhttp://hdl.handle.net/1822/21410
DOI10.1371/journal.pone.0033406
ISSN1932-6203
Versão da editorahttp://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0033406
Arbitragem científicayes
AcessoopenAccess
Aparece nas coleções:ICVS - Artigos em Revistas Internacionais com Referee

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