The pivotal role of 5-lipoxygenase-derived LTB4 in controlling pulmonary paracoccidioidomycosis.
Leukotrienes (LTs) produced from arachidonic acid by the action of 5-lipoxygenase (5-LO) are classical mediators of inflammatory responses. However, studies published in the literature regarding these mediators are contradictory and it remains uncertain whether these lipid mediators play a role in h...
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ftdoajarticles:oai:doaj.org/article:aa270f1eae6942aa9c1ab2a57c339ab9 2023-05-15T15:09:35+02:00 The pivotal role of 5-lipoxygenase-derived LTB4 in controlling pulmonary paracoccidioidomycosis. Patrícia Campi Santos Daniel Assis Santos Lucas Secchim Ribeiro Caio Tavares Fagundes Talles Prosperi de Paula Thiago Vinícius Avila Ludmila de Matos Baltazar Mila Moreira Madeira Rosana de Carvalho Cruz Ana Carolina Fialho Dias Fabiana Simão Machado Mauro Martins Teixeira Patrícia Silva Cisalpino Danielle G Souza 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0002390 https://doaj.org/article/aa270f1eae6942aa9c1ab2a57c339ab9 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC3749973?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002390 https://doaj.org/article/aa270f1eae6942aa9c1ab2a57c339ab9 PLoS Neglected Tropical Diseases, Vol 7, Iss 8, p e2390 (2013) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2013 ftdoajarticles https://doi.org/10.1371/journal.pntd.0002390 2023-01-08T01:28:20Z Leukotrienes (LTs) produced from arachidonic acid by the action of 5-lipoxygenase (5-LO) are classical mediators of inflammatory responses. However, studies published in the literature regarding these mediators are contradictory and it remains uncertain whether these lipid mediators play a role in host defense against the fungal pathogen Paracoccidioides brasiliensis. To determine the involvement of LTs in the host response to pulmonary infection, wild-type and LT-deficient mice by targeted disruption of the 5-lipoxygenase gene (knockout mice) were studied following intratracheal challenge with P. brasiliensis yeasts. The results showed that infection is uniformly fatal in 5-LO-deficient mice and the mechanisms that account for this phenotype are an exacerbated lung injury and higher fungal pulmonary burden. Genetic ablation or pharmacological inhibition of LTs resulted in lower phagocytosis and fungicidal activity of macrophages in vitro, suggesting that deficiency in fungal clearance seems to be secondary to the absence of activation in 5-LO(-/-) macrophages. Exogenous LTB4 restored phagocytosis and fungicidal activity of 5-LO(-/-) macrophages. Moreover, P. brasiliensis killing promoted by LTB4 was dependent on nitric oxide (NO) production by macrophages. Taken together, these results reveal a fundamental role for 5-LO-derived LTB4 in the protective response to P. brasiliensis infection and identify relevant mechanisms for the control of fungal infection during the early stages of the host immune response. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 7 8 e2390 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Patrícia Campi Santos Daniel Assis Santos Lucas Secchim Ribeiro Caio Tavares Fagundes Talles Prosperi de Paula Thiago Vinícius Avila Ludmila de Matos Baltazar Mila Moreira Madeira Rosana de Carvalho Cruz Ana Carolina Fialho Dias Fabiana Simão Machado Mauro Martins Teixeira Patrícia Silva Cisalpino Danielle G Souza The pivotal role of 5-lipoxygenase-derived LTB4 in controlling pulmonary paracoccidioidomycosis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Leukotrienes (LTs) produced from arachidonic acid by the action of 5-lipoxygenase (5-LO) are classical mediators of inflammatory responses. However, studies published in the literature regarding these mediators are contradictory and it remains uncertain whether these lipid mediators play a role in host defense against the fungal pathogen Paracoccidioides brasiliensis. To determine the involvement of LTs in the host response to pulmonary infection, wild-type and LT-deficient mice by targeted disruption of the 5-lipoxygenase gene (knockout mice) were studied following intratracheal challenge with P. brasiliensis yeasts. The results showed that infection is uniformly fatal in 5-LO-deficient mice and the mechanisms that account for this phenotype are an exacerbated lung injury and higher fungal pulmonary burden. Genetic ablation or pharmacological inhibition of LTs resulted in lower phagocytosis and fungicidal activity of macrophages in vitro, suggesting that deficiency in fungal clearance seems to be secondary to the absence of activation in 5-LO(-/-) macrophages. Exogenous LTB4 restored phagocytosis and fungicidal activity of 5-LO(-/-) macrophages. Moreover, P. brasiliensis killing promoted by LTB4 was dependent on nitric oxide (NO) production by macrophages. Taken together, these results reveal a fundamental role for 5-LO-derived LTB4 in the protective response to P. brasiliensis infection and identify relevant mechanisms for the control of fungal infection during the early stages of the host immune response. |
format |
Article in Journal/Newspaper |
author |
Patrícia Campi Santos Daniel Assis Santos Lucas Secchim Ribeiro Caio Tavares Fagundes Talles Prosperi de Paula Thiago Vinícius Avila Ludmila de Matos Baltazar Mila Moreira Madeira Rosana de Carvalho Cruz Ana Carolina Fialho Dias Fabiana Simão Machado Mauro Martins Teixeira Patrícia Silva Cisalpino Danielle G Souza |
author_facet |
Patrícia Campi Santos Daniel Assis Santos Lucas Secchim Ribeiro Caio Tavares Fagundes Talles Prosperi de Paula Thiago Vinícius Avila Ludmila de Matos Baltazar Mila Moreira Madeira Rosana de Carvalho Cruz Ana Carolina Fialho Dias Fabiana Simão Machado Mauro Martins Teixeira Patrícia Silva Cisalpino Danielle G Souza |
author_sort |
Patrícia Campi Santos |
title |
The pivotal role of 5-lipoxygenase-derived LTB4 in controlling pulmonary paracoccidioidomycosis. |
title_short |
The pivotal role of 5-lipoxygenase-derived LTB4 in controlling pulmonary paracoccidioidomycosis. |
title_full |
The pivotal role of 5-lipoxygenase-derived LTB4 in controlling pulmonary paracoccidioidomycosis. |
title_fullStr |
The pivotal role of 5-lipoxygenase-derived LTB4 in controlling pulmonary paracoccidioidomycosis. |
title_full_unstemmed |
The pivotal role of 5-lipoxygenase-derived LTB4 in controlling pulmonary paracoccidioidomycosis. |
title_sort |
pivotal role of 5-lipoxygenase-derived ltb4 in controlling pulmonary paracoccidioidomycosis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2013 |
url |
https://doi.org/10.1371/journal.pntd.0002390 https://doaj.org/article/aa270f1eae6942aa9c1ab2a57c339ab9 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 7, Iss 8, p e2390 (2013) |
op_relation |
http://europepmc.org/articles/PMC3749973?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0002390 https://doaj.org/article/aa270f1eae6942aa9c1ab2a57c339ab9 |
op_doi |
https://doi.org/10.1371/journal.pntd.0002390 |
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PLoS Neglected Tropical Diseases |
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7 |
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8 |
container_start_page |
e2390 |
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