Mycobacterium ulcerans Triggers T-cell immunity followed by local and regional but not systemic immunosuppression
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/18746 |
Resumo: | Buruli ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans, characterized by necrotic cutaneous lesions induced by the exotoxin mycolactone. Despite evidence of Th1-mediated protective immunity, M. ulcerans infection has been associated with systemic immunosuppression. We show that early during mouse infection with either mycolactone-positive or negative strains, pathogen-specific IFN-γ-producing T cells developed in the draining lymph node (DLN). CD4+ cells migrated to infection foci but progressive infection with virulent M. ulcerans led to the local depletion of recruited cells. Moreover, dissemination of virulent M. ulcerans to the DLN was accompanied by extensive DLN apoptotic cytopathology leading to depletion of CD4+ 31 T cells and abrogation of IFN-γ expression. Advanced footpad infection with virulent M. ulcerans did not induce increased susceptibility to systemic co-infection by Listeria monocytogenes. These results show that infection with M. ulcerans efficiently triggers a mycobacteria-specific T cell response in the DLN and that progression of infection with highly virulent M. ulcerans leads to a local and regional suppression of that immune response, but without induction of systemic immunosuppression. These results suggest that prophylactic/therapeutic interventions to prevent dissemination of M. ulcerans to DLN during the early phase of infection would contribute for the maintenance of protective immunity and disease control. |
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Mycobacterium ulcerans Triggers T-cell immunity followed by local and regional but not systemic immunosuppressionBuruli ulcerScience & TechnologyBuruli ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans, characterized by necrotic cutaneous lesions induced by the exotoxin mycolactone. Despite evidence of Th1-mediated protective immunity, M. ulcerans infection has been associated with systemic immunosuppression. We show that early during mouse infection with either mycolactone-positive or negative strains, pathogen-specific IFN-γ-producing T cells developed in the draining lymph node (DLN). CD4+ cells migrated to infection foci but progressive infection with virulent M. ulcerans led to the local depletion of recruited cells. Moreover, dissemination of virulent M. ulcerans to the DLN was accompanied by extensive DLN apoptotic cytopathology leading to depletion of CD4+ 31 T cells and abrogation of IFN-γ expression. Advanced footpad infection with virulent M. ulcerans did not induce increased susceptibility to systemic co-infection by Listeria monocytogenes. These results show that infection with M. ulcerans efficiently triggers a mycobacteria-specific T cell response in the DLN and that progression of infection with highly virulent M. ulcerans leads to a local and regional suppression of that immune response, but without induction of systemic immunosuppression. These results suggest that prophylactic/therapeutic interventions to prevent dissemination of M. ulcerans to DLN during the early phase of infection would contribute for the maintenance of protective immunity and disease control.Fundação Calouste GulbenkianFundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/15911/2005American Society for Microbiology (ASM)Universidade do MinhoFraga, Alexandra G.Cruz, AndreaMartins, Teresa G.Torrado, EgídioSaraiva, MargaridaPereira, Daniela Maria RamosMeyers, Wayne M.Portaels, FrançoiseSilva, Manuel T.Castro, António G.Pedrosa, Jorge2011-012011-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/18746eng0019-956710.1128/IAI.00820-1020974825http://dx.doi.org/10.1128/IAI.00820-10info: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:RCAAP2023-07-21T12:36:01ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Mycobacterium ulcerans Triggers T-cell immunity followed by local and regional but not systemic immunosuppression |
title |
Mycobacterium ulcerans Triggers T-cell immunity followed by local and regional but not systemic immunosuppression |
spellingShingle |
Mycobacterium ulcerans Triggers T-cell immunity followed by local and regional but not systemic immunosuppression Fraga, Alexandra G. Buruli ulcer Science & Technology |
title_short |
Mycobacterium ulcerans Triggers T-cell immunity followed by local and regional but not systemic immunosuppression |
title_full |
Mycobacterium ulcerans Triggers T-cell immunity followed by local and regional but not systemic immunosuppression |
title_fullStr |
Mycobacterium ulcerans Triggers T-cell immunity followed by local and regional but not systemic immunosuppression |
title_full_unstemmed |
Mycobacterium ulcerans Triggers T-cell immunity followed by local and regional but not systemic immunosuppression |
title_sort |
Mycobacterium ulcerans Triggers T-cell immunity followed by local and regional but not systemic immunosuppression |
author |
Fraga, Alexandra G. |
author_facet |
Fraga, Alexandra G. Cruz, Andrea Martins, Teresa G. Torrado, Egídio Saraiva, Margarida Pereira, Daniela Maria Ramos Meyers, Wayne M. Portaels, Françoise Silva, Manuel T. Castro, António G. Pedrosa, Jorge |
author_role |
author |
author2 |
Cruz, Andrea Martins, Teresa G. Torrado, Egídio Saraiva, Margarida Pereira, Daniela Maria Ramos Meyers, Wayne M. Portaels, Françoise Silva, Manuel T. Castro, António G. Pedrosa, Jorge |
author2_role |
author author author 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. Cruz, Andrea Martins, Teresa G. Torrado, Egídio Saraiva, Margarida Pereira, Daniela Maria Ramos Meyers, Wayne M. Portaels, Françoise Silva, Manuel T. Castro, António G. Pedrosa, Jorge |
dc.subject.por.fl_str_mv |
Buruli ulcer Science & Technology |
topic |
Buruli ulcer Science & Technology |
description |
Buruli ulcer (BU) is a neglected infectious disease caused by Mycobacterium ulcerans, characterized by necrotic cutaneous lesions induced by the exotoxin mycolactone. Despite evidence of Th1-mediated protective immunity, M. ulcerans infection has been associated with systemic immunosuppression. We show that early during mouse infection with either mycolactone-positive or negative strains, pathogen-specific IFN-γ-producing T cells developed in the draining lymph node (DLN). CD4+ cells migrated to infection foci but progressive infection with virulent M. ulcerans led to the local depletion of recruited cells. Moreover, dissemination of virulent M. ulcerans to the DLN was accompanied by extensive DLN apoptotic cytopathology leading to depletion of CD4+ 31 T cells and abrogation of IFN-γ expression. Advanced footpad infection with virulent M. ulcerans did not induce increased susceptibility to systemic co-infection by Listeria monocytogenes. These results show that infection with M. ulcerans efficiently triggers a mycobacteria-specific T cell response in the DLN and that progression of infection with highly virulent M. ulcerans leads to a local and regional suppression of that immune response, but without induction of systemic immunosuppression. These results suggest that prophylactic/therapeutic interventions to prevent dissemination of M. ulcerans to DLN during the early phase of infection would contribute for the maintenance of protective immunity and disease control. |
publishDate |
2011 |
dc.date.none.fl_str_mv |
2011-01 2011-01-01T00:00:00Z |
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/1822/18746 |
url |
http://hdl.handle.net/1822/18746 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0019-9567 10.1128/IAI.00820-10 20974825 http://dx.doi.org/10.1128/IAI.00820-10 |
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 |
American Society for Microbiology (ASM) |
publisher.none.fl_str_mv |
American Society for Microbiology (ASM) |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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repository.mail.fl_str_mv |
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_version_ |
1777303796744978432 |