Immune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteins
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/37551 http://dx.doi.org/10.1093/infdis/jit569 |
Resumo: | Leptospirosis is an infectious disease of public health importance. To successfully colonize the host, pathogens have evolved multiple strategies to escape the complement system. Here we demonstrate that the culture supernatant of pathogenic but not saprophytic Leptospira inhibit the three complement pathways. We showed that the proteolytic activity in the supernatants of pathogenic strains targets the central complement molecule C3 and specific proteins from each pathway, such as factor B, C2, and C4b. the proteases cleaved alpha and beta chains of C3 and work in synergy with host regulators to inactivate C3b. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. A recombinant leptospiral metalloprotease from the thermolysin family cleaved C3 in serum and could be one of the proteases responsible for the supernatant activity. We conclude that pathogenic leptospiral proteases can deactivate immune effector molecules and represent potential targets to the development of new therapies in leptospirosis. |
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Fraga, Tatiana RodriguesCourrol, Daniella dos SantosCastiblanco-Valencia, Monica MarcelaHirata, Izaura YoshicoVasconcellos, Slvio ArrudaJuliano, Luiz [UNIFESP]Barbosa, Angela SilvaIsaac, LourdesUniversidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)Butantan Inst2016-01-24T14:35:27Z2016-01-24T14:35:27Z2014-03-15Journal of Infectious Diseases. Cary: Oxford Univ Press Inc, v. 209, n. 6, p. 876-886, 2014.0022-1899http://repositorio.unifesp.br/handle/11600/37551http://dx.doi.org/10.1093/infdis/jit56910.1093/infdis/jit569WOS:000332343600009Leptospirosis is an infectious disease of public health importance. To successfully colonize the host, pathogens have evolved multiple strategies to escape the complement system. Here we demonstrate that the culture supernatant of pathogenic but not saprophytic Leptospira inhibit the three complement pathways. We showed that the proteolytic activity in the supernatants of pathogenic strains targets the central complement molecule C3 and specific proteins from each pathway, such as factor B, C2, and C4b. the proteases cleaved alpha and beta chains of C3 and work in synergy with host regulators to inactivate C3b. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. A recombinant leptospiral metalloprotease from the thermolysin family cleaved C3 in serum and could be one of the proteases responsible for the supernatant activity. We conclude that pathogenic leptospiral proteases can deactivate immune effector molecules and represent potential targets to the development of new therapies in leptospirosis.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508900 São Paulo, BrazilUniv São Paulo, Fac Vet Med, BR-05508900 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilButantan Inst, Lab Bacteriol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilFAPESP: 2010/50043-0Web of Science876-886engOxford Univ Press IncJournal of Infectious Diseaseshttp://www.oxfordjournals.org/access_purchase/self-archiving_policyb.htmlinfo:eu-repo/semantics/openAccessLeptospiraLeptospirosisImmune EvasionInnate ImmunityComplement SystemProteasesImmune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteinsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlereponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/375512023-01-30 22:17:45.671metadata only accessoai:repositorio.unifesp.br:11600/37551Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-01-31T01:17:45Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Immune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteins |
title |
Immune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteins |
spellingShingle |
Immune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteins Fraga, Tatiana Rodrigues Leptospira Leptospirosis Immune Evasion Innate Immunity Complement System Proteases |
title_short |
Immune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteins |
title_full |
Immune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteins |
title_fullStr |
Immune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteins |
title_full_unstemmed |
Immune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteins |
title_sort |
Immune Evasion by Pathogenic Leptospira Strains: the Secretion of Proteases that Directly Cleave Complement Proteins |
author |
Fraga, Tatiana Rodrigues |
author_facet |
Fraga, Tatiana Rodrigues Courrol, Daniella dos Santos Castiblanco-Valencia, Monica Marcela Hirata, Izaura Yoshico Vasconcellos, Slvio Arruda Juliano, Luiz [UNIFESP] Barbosa, Angela Silva Isaac, Lourdes |
author_role |
author |
author2 |
Courrol, Daniella dos Santos Castiblanco-Valencia, Monica Marcela Hirata, Izaura Yoshico Vasconcellos, Slvio Arruda Juliano, Luiz [UNIFESP] Barbosa, Angela Silva Isaac, Lourdes |
author2_role |
author author author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Federal de São Paulo (UNIFESP) Butantan Inst |
dc.contributor.author.fl_str_mv |
Fraga, Tatiana Rodrigues Courrol, Daniella dos Santos Castiblanco-Valencia, Monica Marcela Hirata, Izaura Yoshico Vasconcellos, Slvio Arruda Juliano, Luiz [UNIFESP] Barbosa, Angela Silva Isaac, Lourdes |
dc.subject.eng.fl_str_mv |
Leptospira Leptospirosis Immune Evasion Innate Immunity Complement System Proteases |
topic |
Leptospira Leptospirosis Immune Evasion Innate Immunity Complement System Proteases |
description |
Leptospirosis is an infectious disease of public health importance. To successfully colonize the host, pathogens have evolved multiple strategies to escape the complement system. Here we demonstrate that the culture supernatant of pathogenic but not saprophytic Leptospira inhibit the three complement pathways. We showed that the proteolytic activity in the supernatants of pathogenic strains targets the central complement molecule C3 and specific proteins from each pathway, such as factor B, C2, and C4b. the proteases cleaved alpha and beta chains of C3 and work in synergy with host regulators to inactivate C3b. Proteolytic activity was inhibited by 1,10-phenanthroline, suggesting the participation of metalloproteases. A recombinant leptospiral metalloprotease from the thermolysin family cleaved C3 in serum and could be one of the proteases responsible for the supernatant activity. We conclude that pathogenic leptospiral proteases can deactivate immune effector molecules and represent potential targets to the development of new therapies in leptospirosis. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-03-15 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:35:27Z |
dc.date.available.fl_str_mv |
2016-01-24T14:35:27Z |
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.citation.fl_str_mv |
Journal of Infectious Diseases. Cary: Oxford Univ Press Inc, v. 209, n. 6, p. 876-886, 2014. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/37551 http://dx.doi.org/10.1093/infdis/jit569 |
dc.identifier.issn.none.fl_str_mv |
0022-1899 |
dc.identifier.doi.none.fl_str_mv |
10.1093/infdis/jit569 |
dc.identifier.wos.none.fl_str_mv |
WOS:000332343600009 |
identifier_str_mv |
Journal of Infectious Diseases. Cary: Oxford Univ Press Inc, v. 209, n. 6, p. 876-886, 2014. 0022-1899 10.1093/infdis/jit569 WOS:000332343600009 |
url |
http://repositorio.unifesp.br/handle/11600/37551 http://dx.doi.org/10.1093/infdis/jit569 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Journal of Infectious Diseases |
dc.rights.driver.fl_str_mv |
http://www.oxfordjournals.org/access_purchase/self-archiving_policyb.html info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://www.oxfordjournals.org/access_purchase/self-archiving_policyb.html |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
876-886 |
dc.publisher.none.fl_str_mv |
Oxford Univ Press Inc |
publisher.none.fl_str_mv |
Oxford Univ Press Inc |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
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1802764277579251712 |