Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages
Autor(a) principal: | |
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Data de Publicação: | 2019 |
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/10400.18/6411 |
Resumo: | Nontuberculous Mycobacteria (NTM) respiratory infections have been gradually increasing. Here, THP-1 cells were used as a model to evaluate intracellular persistence of three NTM species (reference and clinical strains) in human alveolar macrophages. The contribution of phagosome acidification, nitric oxide (NO) production and cell dead on NTM intracellular fate was assessed. In addition, strains were characterized regarding their repertoire of virulence factors by whole-genome sequencing. NTM experienced different intracellular fates: M. smegmatis and M. fortuitum ATCC 6841 were cleared within 24h. In contrast, M. avium strains (reference/clinical) and M. fortuitum clinical strain were able to replicate. Despite this fact, unexpectedly high percentages of acidified phagosomes were found harbouring rab7, but not CD63. All NTM were able to survive in vitro at acidic pHs, with the exception of M. smegmatis. Our data further suggested a minor role for NO in intracellular persistence and that apoptosis mediated by caspase 8 and 3/7, but not necrosis, is triggered during NTM infection. Insights regarding the bacteria genomic backbone corroborated the virulence potential of M. avium and M. fortuitum. In conclusion, the phenotypic traits detected contrast with those described for M. tuberculosis, pointing out that NTM adopt distinct strategies to manipulate the host immune defense and persist intracellularly. |
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Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar MacrophagesNontuberculous MycobacteriaHost-pathogen InteractionMacrophagespHVirulenceNTM InfectionRespiratory InfectionsInfecções RespiratóriasAgentes Microbianos e AmbienteNontuberculous Mycobacteria (NTM) respiratory infections have been gradually increasing. Here, THP-1 cells were used as a model to evaluate intracellular persistence of three NTM species (reference and clinical strains) in human alveolar macrophages. The contribution of phagosome acidification, nitric oxide (NO) production and cell dead on NTM intracellular fate was assessed. In addition, strains were characterized regarding their repertoire of virulence factors by whole-genome sequencing. NTM experienced different intracellular fates: M. smegmatis and M. fortuitum ATCC 6841 were cleared within 24h. In contrast, M. avium strains (reference/clinical) and M. fortuitum clinical strain were able to replicate. Despite this fact, unexpectedly high percentages of acidified phagosomes were found harbouring rab7, but not CD63. All NTM were able to survive in vitro at acidic pHs, with the exception of M. smegmatis. Our data further suggested a minor role for NO in intracellular persistence and that apoptosis mediated by caspase 8 and 3/7, but not necrosis, is triggered during NTM infection. Insights regarding the bacteria genomic backbone corroborated the virulence potential of M. avium and M. fortuitum. In conclusion, the phenotypic traits detected contrast with those described for M. tuberculosis, pointing out that NTM adopt distinct strategies to manipulate the host immune defense and persist intracellularly.MDPIRepositório Científico do Instituto Nacional de SaúdeSousa, SaraBorges, VítorJoão, InêsGomes, João PauloJordão, Luisa2019-05-30T09:43:12Z2019-04-262019-04-26T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/6411engMicroorganisms. 2019 Apr 26;7(5). pii: E113. doi: 10.3390/microorganisms70501132076-260710.3390/microorganisms7050113info: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:RCAAP2023-07-20T15:41:24Zoai:repositorio.insa.pt:10400.18/6411Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:41:04.247362Repositório 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 |
Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages |
title |
Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages |
spellingShingle |
Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages Sousa, Sara Nontuberculous Mycobacteria Host-pathogen Interaction Macrophages pH Virulence NTM Infection Respiratory Infections Infecções Respiratórias Agentes Microbianos e Ambiente |
title_short |
Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages |
title_full |
Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages |
title_fullStr |
Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages |
title_full_unstemmed |
Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages |
title_sort |
Nontuberculous Mycobacteria Persistence in a Cell Model Mimicking Alveolar Macrophages |
author |
Sousa, Sara |
author_facet |
Sousa, Sara Borges, Vítor João, Inês Gomes, João Paulo Jordão, Luisa |
author_role |
author |
author2 |
Borges, Vítor João, Inês Gomes, João Paulo Jordão, Luisa |
author2_role |
author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Sousa, Sara Borges, Vítor João, Inês Gomes, João Paulo Jordão, Luisa |
dc.subject.por.fl_str_mv |
Nontuberculous Mycobacteria Host-pathogen Interaction Macrophages pH Virulence NTM Infection Respiratory Infections Infecções Respiratórias Agentes Microbianos e Ambiente |
topic |
Nontuberculous Mycobacteria Host-pathogen Interaction Macrophages pH Virulence NTM Infection Respiratory Infections Infecções Respiratórias Agentes Microbianos e Ambiente |
description |
Nontuberculous Mycobacteria (NTM) respiratory infections have been gradually increasing. Here, THP-1 cells were used as a model to evaluate intracellular persistence of three NTM species (reference and clinical strains) in human alveolar macrophages. The contribution of phagosome acidification, nitric oxide (NO) production and cell dead on NTM intracellular fate was assessed. In addition, strains were characterized regarding their repertoire of virulence factors by whole-genome sequencing. NTM experienced different intracellular fates: M. smegmatis and M. fortuitum ATCC 6841 were cleared within 24h. In contrast, M. avium strains (reference/clinical) and M. fortuitum clinical strain were able to replicate. Despite this fact, unexpectedly high percentages of acidified phagosomes were found harbouring rab7, but not CD63. All NTM were able to survive in vitro at acidic pHs, with the exception of M. smegmatis. Our data further suggested a minor role for NO in intracellular persistence and that apoptosis mediated by caspase 8 and 3/7, but not necrosis, is triggered during NTM infection. Insights regarding the bacteria genomic backbone corroborated the virulence potential of M. avium and M. fortuitum. In conclusion, the phenotypic traits detected contrast with those described for M. tuberculosis, pointing out that NTM adopt distinct strategies to manipulate the host immune defense and persist intracellularly. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-05-30T09:43:12Z 2019-04-26 2019-04-26T00:00:00Z |
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/10400.18/6411 |
url |
http://hdl.handle.net/10400.18/6411 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Microorganisms. 2019 Apr 26;7(5). pii: E113. doi: 10.3390/microorganisms7050113 2076-2607 10.3390/microorganisms7050113 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
MDPI |
publisher.none.fl_str_mv |
MDPI |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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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