Gene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis

dc.creatorCarneiro, Marcia Weber
dc.creatorFukutani, Kiyoshi Ferreira
dc.creatorAndrade, Bruno de Bezerril
dc.creatorCurvelo, Rebecca Pereira
dc.creatorCristal, Juqueline Rocha
dc.creatorCarvalho, Augusto Marcelino Pedreira de
dc.creatorBarral, Aldina Maria Prado
dc.creatorVan Weyenbergh, Johan Jozef Rosa Maria
dc.creatorBarral Netto, Manoel
dc.creatorOliveira, Camila Indiani de
dc.date2017-03-21T18:00:06Z
dc.date2017-03-21T18:00:06Z
dc.date2016
dc.date.accessioned2023-09-27T00:14:27Z
dc.date.available2023-09-27T00:14:27Z
dc.identifierGene Expression Profile of High IFN-γ CARNEIRO, M. W. et al. Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis. PLoS Neglected Tropical Diseases, v. 10, n. 11, p. e0005116, 2016.
dc.identifier1935-2727
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/18109
dc.identifier10.1371/journal.pntd.0005116
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8898856
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grant 302464/2009-3 to M.BN and fellowship to MWC and KFF), Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB) (fellowship to KFF) and Coordenação de Apoio à Pesquisa e Ensino Superior (CAPES)
dc.descriptionThe initial response to Leishmania parasites is essential in determining disease development or resistance. In vitro, a divergent response to Leishmania, characterized by high or low IFN-γ production has been described as a potential tool to predict both vaccine response and disease susceptibility in vivo. Methods and findings We identified uninfected and healthy individuals that were shown to be either high- or low IFN-γ producers (HPs and LPs, respectively) following stimulation of peripheral blood cells with Leishmania braziliensis. Following stimulation, RNA was processed for gene expression analysis using immune gene arrays. Both HPs and LPs were shown to upregulate the expression of CXCL10, IFI27, IL6 and LTA. Genes expressed in HPs only (CCL7, IL8, IFI44L and IL1B) were associated with pathways related to IL17 and TREM 1 signaling. In LPs, uniquely expressed genes (for example IL9, IFI44, IFIT1 and IL2RA) were associated with pathways related to pattern recognition receptors and interferon signaling. We then investigated whether the unique gene expression profiles described here could be recapitulated in vivo, in individuals with active Cutaneous Leishmaniasis or with subclinical infection. Indeed, using a set of six genes (TLR2, JAK2, IFI27, IFIT1, IRF1 and IL6) modulated in HPs and LPs, we could successfully discriminate these two clinical groups. Finally, we demonstrate that these six genes are significantly overexpressed in CL lesions. Conclusion Upon interrogation of the peripheral response of naive individuals with diverging IFN-γ production to L. braziliensis, we identified differences in the innate response to the parasite that are recapitulated in vivo and that discriminate CL patients from individuals presenting a subclinical infection
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectLeishmania braziliensis
dc.subjectLeishmaniose cutânea
dc.subjectGenética
dc.subjectVacina
dc.subjectInfecção
dc.subjectLeishmania braziliensis
dc.subjectCutaneous leishmaniasis
dc.subjectGenetic
dc.subjectVaccine
dc.titleGene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis
dc.typeArticle


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