Cellular immunity confers transient protection in experimental buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination

Detalhes bibliográficos
Autor(a) principal: Fraga, Alexandra G.
Data de Publicação: 2012
Outros Autores: Martins, Teresa G., Torrado, Egídio, Huygen, Kris, Portaels, Françoise, Silva, Manuel T., Castro, António G., Pedrosa, Jorge
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/21410
Resumo: The 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.
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spelling Cellular immunity confers transient protection in experimental buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccinationBuruli ulcerMycobacterium ulceransCell-mediated immune responseTh1 responseScience & TechnologyThe 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.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.The research leading to these results has received funding from the European Community’s Seventh Framework Program (FP7/2007–2013) under grant agreement Nu 241500 (BuruliVac). This work was additionally supported by a Grant from the Health Services of Fundação Calouste Gulbenkian, and by thePortuguese Science and Technology Foundation (FCT) fellowships SFRH/BPD/68547/2010, SFRH/BD/41598/2007 to A. G. Fraga and T. G. Martins.Public Library of ScienceUniversidade do MinhoFraga, Alexandra G.Martins, Teresa G.Torrado, EgídioHuygen, KrisPortaels, FrançoiseSilva, Manuel T.Castro, António G.Pedrosa, Jorge2012-032012-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/21410eng1932-620310.1371/journal.pone.003340622413022http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0033406info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:32:18Zoai:repositorium.sdum.uminho.pt:1822/21410Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:27:37.725880Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Cellular immunity confers transient protection in experimental buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination
title Cellular immunity confers transient protection in experimental buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination
spellingShingle Cellular immunity confers transient protection in experimental buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination
Fraga, Alexandra G.
Buruli ulcer
Mycobacterium ulcerans
Cell-mediated immune response
Th1 response
Science & Technology
title_short Cellular immunity confers transient protection in experimental buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination
title_full Cellular immunity confers transient protection in experimental buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination
title_fullStr Cellular immunity confers transient protection in experimental buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination
title_full_unstemmed Cellular immunity confers transient protection in experimental buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination
title_sort Cellular immunity confers transient protection in experimental buruli ulcer following BCG or mycolactone-negative Mycobacterium ulcerans vaccination
author Fraga, Alexandra G.
author_facet Fraga, Alexandra G.
Martins, Teresa G.
Torrado, Egídio
Huygen, Kris
Portaels, Françoise
Silva, Manuel T.
Castro, António G.
Pedrosa, Jorge
author_role author
author2 Martins, Teresa G.
Torrado, Egídio
Huygen, Kris
Portaels, Françoise
Silva, Manuel T.
Castro, António G.
Pedrosa, Jorge
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Fraga, Alexandra G.
Martins, Teresa G.
Torrado, Egídio
Huygen, Kris
Portaels, Françoise
Silva, Manuel T.
Castro, António G.
Pedrosa, Jorge
dc.subject.por.fl_str_mv Buruli ulcer
Mycobacterium ulcerans
Cell-mediated immune response
Th1 response
Science & Technology
topic Buruli ulcer
Mycobacterium ulcerans
Cell-mediated immune response
Th1 response
Science & Technology
description The 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.
publishDate 2012
dc.date.none.fl_str_mv 2012-03
2012-03-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/21410
url http://hdl.handle.net/1822/21410
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1932-6203
10.1371/journal.pone.0033406
22413022
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0033406
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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