The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis
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 UNESP |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0085083 http://hdl.handle.net/11449/112064 |
Resumo: | The bioactive lipid mediator leukotriene B-4 (LTB4) greatly enhances phagocyte antimicrobial functions against a myriad of pathogens. In murine histoplasmosis, inhibition of the LT-generating enzyme 5-lypoxigenase (5-LO) increases the susceptibility of the host to infection. In this study, we investigated whether murine resistance or susceptibility to Histoplasma capsulatum infection is associated with leukotriene production and an enhancement of in vivo and/or in vitro antimicrobial effector function. We show that susceptible C57BL/6 mice exhibit a higher fungal burden in the lung and spleen, increased mortality, lower expression levels of 5-LO and leukotriene B-4 receptor 1 (BLT1) and decreased LTB4 production compared to the resistant 129/Sv mice. Moreover, we demonstrate that endogenous and exogenous LTs are required for the optimal phagocytosis of H. capsulatum by macrophages from both murine strains, although C57BL/6 macrophages are more sensitive to the effects of LTB4 than 129/Sv macrophages. Therefore, our results provide novel evidence that LTB4 production and BLT1 signaling are required for a histoplasmosis-resistant phenotype. |
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The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to HistoplasmosisThe bioactive lipid mediator leukotriene B-4 (LTB4) greatly enhances phagocyte antimicrobial functions against a myriad of pathogens. In murine histoplasmosis, inhibition of the LT-generating enzyme 5-lypoxigenase (5-LO) increases the susceptibility of the host to infection. In this study, we investigated whether murine resistance or susceptibility to Histoplasma capsulatum infection is associated with leukotriene production and an enhancement of in vivo and/or in vitro antimicrobial effector function. We show that susceptible C57BL/6 mice exhibit a higher fungal burden in the lung and spleen, increased mortality, lower expression levels of 5-LO and leukotriene B-4 receptor 1 (BLT1) and decreased LTB4 production compared to the resistant 129/Sv mice. Moreover, we demonstrate that endogenous and exogenous LTs are required for the optimal phagocytosis of H. capsulatum by macrophages from both murine strains, although C57BL/6 macrophages are more sensitive to the effects of LTB4 than 129/Sv macrophages. Therefore, our results provide novel evidence that LTB4 production and BLT1 signaling are required for a histoplasmosis-resistant phenotype.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Institutes of Health (NIH)Univ Sao Paulo, Dept Anal Clin Toxicol & Bromatol, Fac Ciencias Farmaceut Ribeirao Preto, Sao Paulo, BrazilUniv Sao Paulo, Dept Odontopediat, Fac Odontol Ribeirao Preto, Sao Paulo, BrazilIndiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USAUniv Estadual Paulista, Dept Ciencias Biol, Fac Ciencias Farmaceut, Sao Paulo, BrazilUniv Estadual Paulista, Dept Ciencias Biol, Fac Ciencias Farmaceut, Sao Paulo, BrazilCNPq: 302097/2010-4National Institutes of Health (NIH)HL103777-04Public Library ScienceUniversidade de São Paulo (USP)Indiana UniversityUniversidade Estadual Paulista (Unesp)Secatto, AdrianaSoares, Elyara MariaLocachevic, Gisele AparecidaAssis, Patricia AparecidaGarcia Paula-Silva, Francisco WanderleiSerezani, Carlos HenriqueMedeiros, Alexandra Ivo de [UNESP]Faccioli, Lucia Helena2014-12-03T13:09:12Z2014-12-03T13:09:12Z2014-01-21info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article9application/pdfhttp://dx.doi.org/10.1371/journal.pone.0085083Plos One. San Francisco: Public Library Science, v. 9, n. 1, 9 p., 2014.1932-6203http://hdl.handle.net/11449/11206410.1371/journal.pone.0085083WOS:000330244500034WOS000330244500034.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPLOS ONE2.7661,164info:eu-repo/semantics/openAccess2024-06-24T13:07:51Zoai:repositorio.unesp.br:11449/112064Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T19:12:01.072942Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis |
title |
The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis |
spellingShingle |
The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis Secatto, Adriana |
title_short |
The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis |
title_full |
The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis |
title_fullStr |
The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis |
title_full_unstemmed |
The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis |
title_sort |
The Leukotriene B-4/BLT1 Axis Is a Key Determinant in Susceptibility and Resistance to Histoplasmosis |
author |
Secatto, Adriana |
author_facet |
Secatto, Adriana Soares, Elyara Maria Locachevic, Gisele Aparecida Assis, Patricia Aparecida Garcia Paula-Silva, Francisco Wanderlei Serezani, Carlos Henrique Medeiros, Alexandra Ivo de [UNESP] Faccioli, Lucia Helena |
author_role |
author |
author2 |
Soares, Elyara Maria Locachevic, Gisele Aparecida Assis, Patricia Aparecida Garcia Paula-Silva, Francisco Wanderlei Serezani, Carlos Henrique Medeiros, Alexandra Ivo de [UNESP] Faccioli, Lucia Helena |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Indiana University Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Secatto, Adriana Soares, Elyara Maria Locachevic, Gisele Aparecida Assis, Patricia Aparecida Garcia Paula-Silva, Francisco Wanderlei Serezani, Carlos Henrique Medeiros, Alexandra Ivo de [UNESP] Faccioli, Lucia Helena |
description |
The bioactive lipid mediator leukotriene B-4 (LTB4) greatly enhances phagocyte antimicrobial functions against a myriad of pathogens. In murine histoplasmosis, inhibition of the LT-generating enzyme 5-lypoxigenase (5-LO) increases the susceptibility of the host to infection. In this study, we investigated whether murine resistance or susceptibility to Histoplasma capsulatum infection is associated with leukotriene production and an enhancement of in vivo and/or in vitro antimicrobial effector function. We show that susceptible C57BL/6 mice exhibit a higher fungal burden in the lung and spleen, increased mortality, lower expression levels of 5-LO and leukotriene B-4 receptor 1 (BLT1) and decreased LTB4 production compared to the resistant 129/Sv mice. Moreover, we demonstrate that endogenous and exogenous LTs are required for the optimal phagocytosis of H. capsulatum by macrophages from both murine strains, although C57BL/6 macrophages are more sensitive to the effects of LTB4 than 129/Sv macrophages. Therefore, our results provide novel evidence that LTB4 production and BLT1 signaling are required for a histoplasmosis-resistant phenotype. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-12-03T13:09:12Z 2014-12-03T13:09:12Z 2014-01-21 |
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://dx.doi.org/10.1371/journal.pone.0085083 Plos One. San Francisco: Public Library Science, v. 9, n. 1, 9 p., 2014. 1932-6203 http://hdl.handle.net/11449/112064 10.1371/journal.pone.0085083 WOS:000330244500034 WOS000330244500034.pdf |
url |
http://dx.doi.org/10.1371/journal.pone.0085083 http://hdl.handle.net/11449/112064 |
identifier_str_mv |
Plos One. San Francisco: Public Library Science, v. 9, n. 1, 9 p., 2014. 1932-6203 10.1371/journal.pone.0085083 WOS:000330244500034 WOS000330244500034.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLOS ONE 2.766 1,164 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
9 application/pdf |
dc.publisher.none.fl_str_mv |
Public Library Science |
publisher.none.fl_str_mv |
Public Library Science |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808129032027373568 |