Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice
Autor(a) principal: | |
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Data de Publicação: | 2014 |
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/1822/32213 |
Resumo: | The production of antimicrobial peptides, such as the cathelicidins, plays a prominent role in the innate immune response against microbial pathogens. Cathelicidins are widely distributed amongst living organisms, and the antimicrobial peptides generated by proteolysis of the precursor forms are typically cationic and [alpha]-helical, a structure that facilitates their interaction and insertion into anionic bacterial cell walls and membranes, causing damage and promoting microbial death. Here, we found that mouse cathelicidin (Camp) expression was induced in bone marrow-derived macrophages by infection with Mycobacterium avium in a TLR2- and TNF-dependent manner. However, the endogenous production of the cathelin-related antimicrobial peptide (CRAMP) was not required for the bacteriostasis of M. avium either in primary cultures of macrophages or in vivo, as shown by the use of CRAMP-null mice. In contrast, the lack of Camp led to a transient improvement of M. avium growth control in the spleens of infected mice while at the same time causing an exacerbation of the inflammatory response to infection. Our data highlight the anti-inflammatory effects of CRAMP and suggests that virulent mycobacteria may possess strategies to escape its antimicrobial activity. |
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Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in miceCathelicidinMycobacteriumAntimicrobial peptidesmacrophageScience & TechnologyThe production of antimicrobial peptides, such as the cathelicidins, plays a prominent role in the innate immune response against microbial pathogens. Cathelicidins are widely distributed amongst living organisms, and the antimicrobial peptides generated by proteolysis of the precursor forms are typically cationic and [alpha]-helical, a structure that facilitates their interaction and insertion into anionic bacterial cell walls and membranes, causing damage and promoting microbial death. Here, we found that mouse cathelicidin (Camp) expression was induced in bone marrow-derived macrophages by infection with Mycobacterium avium in a TLR2- and TNF-dependent manner. However, the endogenous production of the cathelin-related antimicrobial peptide (CRAMP) was not required for the bacteriostasis of M. avium either in primary cultures of macrophages or in vivo, as shown by the use of CRAMP-null mice. In contrast, the lack of Camp led to a transient improvement of M. avium growth control in the spleens of infected mice while at the same time causing an exacerbation of the inflammatory response to infection. Our data highlight the anti-inflammatory effects of CRAMP and suggests that virulent mycobacteria may possess strategies to escape its antimicrobial activity.Funded through project PTDC/BIA-BCM/112138/2009FCOMP-01-0124-FEDER014185.WileyUniversidade do MinhoSantos, J. C.Silva-Gomes, S.Silva, João P.Gama, F. M.Rosa, G.Gallo, R. L.Appelberg, R.20142014-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/32213engSantos, J. C.; Silva-Gomes, S.; Silva, João P.; Gama, F. M.; Rosa, G.; Gallo, R. L.; Appelberg, R., Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice. Immunity, Inflammation and Disease, 2(1), 1-12, 20142050-45272050-452710.1002/iid3.7http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2050-4527info: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:RCAAP2023-07-21T12:42:01Zoai:repositorium.sdum.uminho.pt:1822/32213Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:39:10.726957Repositório 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 |
Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice |
title |
Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice |
spellingShingle |
Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice Santos, J. C. Cathelicidin Mycobacterium Antimicrobial peptides macrophage Science & Technology |
title_short |
Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice |
title_full |
Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice |
title_fullStr |
Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice |
title_full_unstemmed |
Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice |
title_sort |
Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice |
author |
Santos, J. C. |
author_facet |
Santos, J. C. Silva-Gomes, S. Silva, João P. Gama, F. M. Rosa, G. Gallo, R. L. Appelberg, R. |
author_role |
author |
author2 |
Silva-Gomes, S. Silva, João P. Gama, F. M. Rosa, G. Gallo, R. L. Appelberg, R. |
author2_role |
author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Santos, J. C. Silva-Gomes, S. Silva, João P. Gama, F. M. Rosa, G. Gallo, R. L. Appelberg, R. |
dc.subject.por.fl_str_mv |
Cathelicidin Mycobacterium Antimicrobial peptides macrophage Science & Technology |
topic |
Cathelicidin Mycobacterium Antimicrobial peptides macrophage Science & Technology |
description |
The production of antimicrobial peptides, such as the cathelicidins, plays a prominent role in the innate immune response against microbial pathogens. Cathelicidins are widely distributed amongst living organisms, and the antimicrobial peptides generated by proteolysis of the precursor forms are typically cationic and [alpha]-helical, a structure that facilitates their interaction and insertion into anionic bacterial cell walls and membranes, causing damage and promoting microbial death. Here, we found that mouse cathelicidin (Camp) expression was induced in bone marrow-derived macrophages by infection with Mycobacterium avium in a TLR2- and TNF-dependent manner. However, the endogenous production of the cathelin-related antimicrobial peptide (CRAMP) was not required for the bacteriostasis of M. avium either in primary cultures of macrophages or in vivo, as shown by the use of CRAMP-null mice. In contrast, the lack of Camp led to a transient improvement of M. avium growth control in the spleens of infected mice while at the same time causing an exacerbation of the inflammatory response to infection. Our data highlight the anti-inflammatory effects of CRAMP and suggests that virulent mycobacteria may possess strategies to escape its antimicrobial activity. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014 2014-01-01T00:00:00Z |
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/1822/32213 |
url |
http://hdl.handle.net/1822/32213 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Santos, J. C.; Silva-Gomes, S.; Silva, João P.; Gama, F. M.; Rosa, G.; Gallo, R. L.; Appelberg, R., Endogenous cathelicidin production limits inflammation and protective immunity to Mycobacterium avium in mice. Immunity, Inflammation and Disease, 2(1), 1-12, 2014 2050-4527 2050-4527 10.1002/iid3.7 http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2050-4527 |
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 |
Wiley |
publisher.none.fl_str_mv |
Wiley |
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 |
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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 |
repository.mail.fl_str_mv |
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1799132931102343168 |