Mycolactone-mediated inhibition of tumor necrosis factor production by macrophages infected with Mycobacterium ulcerans has implications for the control of infection
Autor(a) principal: | |
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Data de Publicação: | 2007 |
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/1822/67770 |
Resumo: | The pathogenicity of Mycobacterium ulcerans, the agent of Buruli ulcer, depends on the cytotoxic exotoxin mycolactone. Little is known about the immune response to this pathogen. Following the demonstration of an intracellular growth phase in the life cycle of M. ulcerans, we investigated the production of tumor necrosis factor (TNF) induced by intramacrophage bacilli of diverse toxigenesis/virulence, as well as the biological relevance of TNF during M. ulcerans experimental infections. Our data show that murine bone marrow-derived macrophages infected with mycolactone-negative strains of M. ulcerans (nonvirulent) produce high amounts of TNF, while macrophages infected with mycolactone-positive strains of intermediate or high virulence produce intermediate or low amounts of TNF, respectively. These results are in accordance with the finding that TNF receptor P55-deficient (TNF-P55 KO) mice are not more susceptible than wild-type mice to infection by the highly virulent strains but are more susceptible to nonvirulent and intermediately virulent strains, demonstrating that TNF is required to control the proliferation of these strains in animals experimentally infected by M. ulcerans. We also show that mycolactone produced by intramacrophage M. ulcerans bacilli inhibits, in a dose-dependent manner, but does not abrogate, the production of macrophage inflammatory protein 2, which is consistent with the persistent inflammatory responses observed in experimentally infected mice. |
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Mycolactone-mediated inhibition of tumor necrosis factor production by macrophages infected with Mycobacterium ulcerans has implications for the control of infectionAnimalsBacterial ToxinsCells, CulturedChemokine CXCL2Disease Models, AnimalFemaleFootMacrolidesMacrophagesMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMonokinesMycobacterium Infections, NontuberculousMycobacterium ulceransReceptors, Tumor Necrosis Factor, Type ITumor Necrosis Factor Decoy ReceptorsTumor Necrosis Factor-alphaVirulenceScience & TechnologyThe pathogenicity of Mycobacterium ulcerans, the agent of Buruli ulcer, depends on the cytotoxic exotoxin mycolactone. Little is known about the immune response to this pathogen. Following the demonstration of an intracellular growth phase in the life cycle of M. ulcerans, we investigated the production of tumor necrosis factor (TNF) induced by intramacrophage bacilli of diverse toxigenesis/virulence, as well as the biological relevance of TNF during M. ulcerans experimental infections. Our data show that murine bone marrow-derived macrophages infected with mycolactone-negative strains of M. ulcerans (nonvirulent) produce high amounts of TNF, while macrophages infected with mycolactone-positive strains of intermediate or high virulence produce intermediate or low amounts of TNF, respectively. These results are in accordance with the finding that TNF receptor P55-deficient (TNF-P55 KO) mice are not more susceptible than wild-type mice to infection by the highly virulent strains but are more susceptible to nonvirulent and intermediately virulent strains, demonstrating that TNF is required to control the proliferation of these strains in animals experimentally infected by M. ulcerans. We also show that mycolactone produced by intramacrophage M. ulcerans bacilli inhibits, in a dose-dependent manner, but does not abrogate, the production of macrophage inflammatory protein 2, which is consistent with the persistent inflammatory responses observed in experimentally infected mice.This work was supported by a grant from the Health Services of Fundação Calouste Gulbenkian and by FCT Fellowships Praxis SFRH/ BD/9757/2003 and SFRH/BD/15911/2005 to E. Torrado and A. G. Fraga, respectivelyAmerican Society for Microbiology (ASM)Universidade do MinhoTorrado, EgídioAdusumilli, SarojiniFraga, Alexandra GabrielSmall, Pamela L. C.Castro, António G.Pedrosa, Jorge2007-082007-08-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/67770eng0019-95671098-552210.1128/IAI.00290-0717517872info: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:RCAAP2023-07-21T12:34:37ZPortal AgregadorONG |
dc.title.none.fl_str_mv |
Mycolactone-mediated inhibition of tumor necrosis factor production by macrophages infected with Mycobacterium ulcerans has implications for the control of infection |
title |
Mycolactone-mediated inhibition of tumor necrosis factor production by macrophages infected with Mycobacterium ulcerans has implications for the control of infection |
spellingShingle |
Mycolactone-mediated inhibition of tumor necrosis factor production by macrophages infected with Mycobacterium ulcerans has implications for the control of infection Torrado, Egídio Animals Bacterial Toxins Cells, Cultured Chemokine CXCL2 Disease Models, Animal Female Foot Macrolides Macrophages Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Monokines Mycobacterium Infections, Nontuberculous Mycobacterium ulcerans Receptors, Tumor Necrosis Factor, Type I Tumor Necrosis Factor Decoy Receptors Tumor Necrosis Factor-alpha Virulence Science & Technology |
title_short |
Mycolactone-mediated inhibition of tumor necrosis factor production by macrophages infected with Mycobacterium ulcerans has implications for the control of infection |
title_full |
Mycolactone-mediated inhibition of tumor necrosis factor production by macrophages infected with Mycobacterium ulcerans has implications for the control of infection |
title_fullStr |
Mycolactone-mediated inhibition of tumor necrosis factor production by macrophages infected with Mycobacterium ulcerans has implications for the control of infection |
title_full_unstemmed |
Mycolactone-mediated inhibition of tumor necrosis factor production by macrophages infected with Mycobacterium ulcerans has implications for the control of infection |
title_sort |
Mycolactone-mediated inhibition of tumor necrosis factor production by macrophages infected with Mycobacterium ulcerans has implications for the control of infection |
author |
Torrado, Egídio |
author_facet |
Torrado, Egídio Adusumilli, Sarojini Fraga, Alexandra Gabriel Small, Pamela L. C. Castro, António G. Pedrosa, Jorge |
author_role |
author |
author2 |
Adusumilli, Sarojini Fraga, Alexandra Gabriel Small, Pamela L. C. Castro, António G. Pedrosa, Jorge |
author2_role |
author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Torrado, Egídio Adusumilli, Sarojini Fraga, Alexandra Gabriel Small, Pamela L. C. Castro, António G. Pedrosa, Jorge |
dc.subject.por.fl_str_mv |
Animals Bacterial Toxins Cells, Cultured Chemokine CXCL2 Disease Models, Animal Female Foot Macrolides Macrophages Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Monokines Mycobacterium Infections, Nontuberculous Mycobacterium ulcerans Receptors, Tumor Necrosis Factor, Type I Tumor Necrosis Factor Decoy Receptors Tumor Necrosis Factor-alpha Virulence Science & Technology |
topic |
Animals Bacterial Toxins Cells, Cultured Chemokine CXCL2 Disease Models, Animal Female Foot Macrolides Macrophages Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Monokines Mycobacterium Infections, Nontuberculous Mycobacterium ulcerans Receptors, Tumor Necrosis Factor, Type I Tumor Necrosis Factor Decoy Receptors Tumor Necrosis Factor-alpha Virulence Science & Technology |
description |
The pathogenicity of Mycobacterium ulcerans, the agent of Buruli ulcer, depends on the cytotoxic exotoxin mycolactone. Little is known about the immune response to this pathogen. Following the demonstration of an intracellular growth phase in the life cycle of M. ulcerans, we investigated the production of tumor necrosis factor (TNF) induced by intramacrophage bacilli of diverse toxigenesis/virulence, as well as the biological relevance of TNF during M. ulcerans experimental infections. Our data show that murine bone marrow-derived macrophages infected with mycolactone-negative strains of M. ulcerans (nonvirulent) produce high amounts of TNF, while macrophages infected with mycolactone-positive strains of intermediate or high virulence produce intermediate or low amounts of TNF, respectively. These results are in accordance with the finding that TNF receptor P55-deficient (TNF-P55 KO) mice are not more susceptible than wild-type mice to infection by the highly virulent strains but are more susceptible to nonvirulent and intermediately virulent strains, demonstrating that TNF is required to control the proliferation of these strains in animals experimentally infected by M. ulcerans. We also show that mycolactone produced by intramacrophage M. ulcerans bacilli inhibits, in a dose-dependent manner, but does not abrogate, the production of macrophage inflammatory protein 2, which is consistent with the persistent inflammatory responses observed in experimentally infected mice. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-08 2007-08-01T00:00:00Z |
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/1822/67770 |
url |
http://hdl.handle.net/1822/67770 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0019-9567 1098-5522 10.1128/IAI.00290-07 17517872 |
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 |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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1777303790617100288 |