Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species
Autor(a) principal: | |
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Data de Publicação: | 2013 |
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/10400.22/6050 |
Resumo: | Iron plays a central role in host-parasite interactions, since both intervenients need iron for survival and growth, but are sensitive to iron-mediated toxicity. The host’s iron overload is often associated with susceptibility to infection. However, it has been previously reported that iron overload prevented the growth of Leishmania major, an agent of cutaneous leishmaniasis, in BALB/c mice. In order to further clarify the impact of iron modulation on the growth of Leishmania in vivo, we studied the effects of iron supplementation or deprivation on the growth of L. infantum, the causative agent of Mediterranean visceral leishmaniasis, in the mouse model. We found that dietary iron deficiency did not affect the protozoan growth, whereas iron overload decreased its replication in the liver and spleen of a susceptible mouse strain. The fact that the iron-induced inhibitory effect could not be seen in mice deficient in NADPH dependent oxidase or nitric oxide synthase 2 suggests that iron eliminates L. infantum in vivo through the interaction with reactive oxygen and nitrogen species. Iron overload did not significantly alter the mouse adaptive immune response against L. infantum. Furthermore, the inhibitory action of iron towards L. infantum was also observed, in a dose dependent manner, in axenic cultures of promastigotes and amastigotes. Importantly, high iron concentrations were needed to achieve such effects. In conclusion, externally added iron synergizes with the host’s oxidative mechanisms of defense in eliminating L. infantum from mouse tissues. Additionally, the direct toxicity of iron against Leishmania suggests a potential use of this metal as a therapeutic tool or the further exploration of iron anti-parasitic mechanisms for the design of new drugs. |
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Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen SpeciesIron plays a central role in host-parasite interactions, since both intervenients need iron for survival and growth, but are sensitive to iron-mediated toxicity. The host’s iron overload is often associated with susceptibility to infection. However, it has been previously reported that iron overload prevented the growth of Leishmania major, an agent of cutaneous leishmaniasis, in BALB/c mice. In order to further clarify the impact of iron modulation on the growth of Leishmania in vivo, we studied the effects of iron supplementation or deprivation on the growth of L. infantum, the causative agent of Mediterranean visceral leishmaniasis, in the mouse model. We found that dietary iron deficiency did not affect the protozoan growth, whereas iron overload decreased its replication in the liver and spleen of a susceptible mouse strain. The fact that the iron-induced inhibitory effect could not be seen in mice deficient in NADPH dependent oxidase or nitric oxide synthase 2 suggests that iron eliminates L. infantum in vivo through the interaction with reactive oxygen and nitrogen species. Iron overload did not significantly alter the mouse adaptive immune response against L. infantum. Furthermore, the inhibitory action of iron towards L. infantum was also observed, in a dose dependent manner, in axenic cultures of promastigotes and amastigotes. Importantly, high iron concentrations were needed to achieve such effects. In conclusion, externally added iron synergizes with the host’s oxidative mechanisms of defense in eliminating L. infantum from mouse tissues. Additionally, the direct toxicity of iron against Leishmania suggests a potential use of this metal as a therapeutic tool or the further exploration of iron anti-parasitic mechanisms for the design of new drugs.PLoS Neglected Tropical DiseasesRepositório Científico do Instituto Politécnico do PortoVale-Costa, SílviaGomes Pereira, Sandra IsabelTeixeira, Carlos MiguelRosa, GustavoRodrigues, Pedro NunoTomás, AnaAppelberg, RuiGomes, Maria Salomé2015-05-18T13:56:13Z20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.22/6050eng10.1371/journal.pntd.0002061info: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:RCAAP2023-03-13T12:46:15Zoai:recipp.ipp.pt:10400.22/6050Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:26:39.998976Repositório 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 |
Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species |
title |
Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species |
spellingShingle |
Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species Vale-Costa, Sílvia |
title_short |
Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species |
title_full |
Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species |
title_fullStr |
Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species |
title_full_unstemmed |
Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species |
title_sort |
Iron Overload Favors the Elimination of Leishmania infantum from Mouse Tissues through Interaction with Reactive Oxygen and Nitrogen Species |
author |
Vale-Costa, Sílvia |
author_facet |
Vale-Costa, Sílvia Gomes Pereira, Sandra Isabel Teixeira, Carlos Miguel Rosa, Gustavo Rodrigues, Pedro Nuno Tomás, Ana Appelberg, Rui Gomes, Maria Salomé |
author_role |
author |
author2 |
Gomes Pereira, Sandra Isabel Teixeira, Carlos Miguel Rosa, Gustavo Rodrigues, Pedro Nuno Tomás, Ana Appelberg, Rui Gomes, Maria Salomé |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Politécnico do Porto |
dc.contributor.author.fl_str_mv |
Vale-Costa, Sílvia Gomes Pereira, Sandra Isabel Teixeira, Carlos Miguel Rosa, Gustavo Rodrigues, Pedro Nuno Tomás, Ana Appelberg, Rui Gomes, Maria Salomé |
description |
Iron plays a central role in host-parasite interactions, since both intervenients need iron for survival and growth, but are sensitive to iron-mediated toxicity. The host’s iron overload is often associated with susceptibility to infection. However, it has been previously reported that iron overload prevented the growth of Leishmania major, an agent of cutaneous leishmaniasis, in BALB/c mice. In order to further clarify the impact of iron modulation on the growth of Leishmania in vivo, we studied the effects of iron supplementation or deprivation on the growth of L. infantum, the causative agent of Mediterranean visceral leishmaniasis, in the mouse model. We found that dietary iron deficiency did not affect the protozoan growth, whereas iron overload decreased its replication in the liver and spleen of a susceptible mouse strain. The fact that the iron-induced inhibitory effect could not be seen in mice deficient in NADPH dependent oxidase or nitric oxide synthase 2 suggests that iron eliminates L. infantum in vivo through the interaction with reactive oxygen and nitrogen species. Iron overload did not significantly alter the mouse adaptive immune response against L. infantum. Furthermore, the inhibitory action of iron towards L. infantum was also observed, in a dose dependent manner, in axenic cultures of promastigotes and amastigotes. Importantly, high iron concentrations were needed to achieve such effects. In conclusion, externally added iron synergizes with the host’s oxidative mechanisms of defense in eliminating L. infantum from mouse tissues. Additionally, the direct toxicity of iron against Leishmania suggests a potential use of this metal as a therapeutic tool or the further exploration of iron anti-parasitic mechanisms for the design of new drugs. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013 2013-01-01T00:00:00Z 2015-05-18T13:56:13Z |
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/10400.22/6050 |
url |
http://hdl.handle.net/10400.22/6050 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1371/journal.pntd.0002061 |
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 |
PLoS Neglected Tropical Diseases |
publisher.none.fl_str_mv |
PLoS Neglected Tropical Diseases |
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 |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
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 |
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1799131361173307392 |