5-Lipoxygenase Deficiency Impairs Innate and Adaptive Immune Responses during Fungal Infection

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dc.contributor.authorSecatto, Adriana
dc.contributor.authorRodrigues, Lilian Cataldi
dc.contributor.authorSerezani, Carlos Henrique
dc.contributor.authorRamos, Simone Gusmao
dc.contributor.authorDias-Baruffi, Marcelo
dc.contributor.authorFaccioli, Lucia Helena
dc.contributor.authorMedeiros, Alexandra Ivo de [UNESP]
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversity of Michigan
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-20T15:34:08Z
dc.date.available2014-05-20T15:34:08Z
dc.date.issued2012-03-20
dc.description.abstract5-lipoxygenase-derived products have been implicated in both the inhibition and promotion of chronic infection. Here, we sought to investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection in vivo and in vitro. 5-LO deficiency led to increased lung CFU, decreased nitric oxide production and a deficient primary immune response during active fungal infection. Moreover, H. capsulatum-infected 5-LO-/- mice showed an intense influx of neutrophils and an impaired ability to generate and recruit effector T cells to the lung. The fungal susceptibility of 5-LO-/- mice correlated with a lower rate of macrophage ingestion of IgG-H. capsulatum relative to WT macrophages. Conversely, exogenous LTB4 and LTC4 restored macrophage phagocytosis in 5-LO deficient mice. Our results demonstrate that leukotrienes are required to control chronic fungal infection by amplifying both the innate and adaptive immune response during histoplasmosis.en
dc.description.affiliationUniv São Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Anal Clin Toxicol & Bromatol, São Paulo, Brazil
dc.description.affiliationUniv Michigan Hlth Syst, Dept Internal Med, Div Pulm & Crit Care Med, Ann Arbor, MI USA
dc.description.affiliationUniv São Paulo, Fac Med Ribeirao Preto, Dept Patol, São Paulo, Brazil
dc.description.affiliationUniv Estadual Paulista, Fac Ciencias Farmaceut, Dept Ciencias Biol, São Paulo, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Fac Ciencias Farmaceut, Dept Ciencias Biol, São Paulo, Brazil
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipNational Institutes of Health (NIH)
dc.description.sponsorshipIdNIH: HL-103777 01
dc.format.extent9
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0031701
dc.identifier.citationPlos One. San Francisco: Public Library Science, v. 7, n. 3, p. 9, 2012.
dc.identifier.doi10.1371/journal.pone.0031701
dc.identifier.fileWOS000303855700003.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttp://hdl.handle.net/11449/42431
dc.identifier.wosWOS:000303855700003
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPLOS ONE
dc.relation.ispartofjcr2.766
dc.relation.ispartofsjr1,164
dc.rights.accessRightsAcesso aberto
dc.sourceWeb of Science
dc.title5-Lipoxygenase Deficiency Impairs Innate and Adaptive Immune Responses during Fungal Infectionen
dc.typeArtigo
dcterms.licensehttp://www.plos.org/about/open-access/license/
dcterms.rightsHolderPublic Library Science
unesp.author.lattes8756770929017974[7]
unesp.author.orcid0000-0002-5363-415X[3]
unesp.author.orcid0000-0001-6048-3647[7]
unesp.author.orcid0000-0002-2039-1884[5]
unesp.author.orcid0000-0002-4999-8305[6]
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Ciências Farmacêuticas, Araraquarapt

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Artigos - Ciências Biológicas - FCFAR