Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/18109
Title: Gene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis
Authors: Carneiro, Marcia Weber
Fukutani, Kiyoshi Ferreira
Andrade, Bruno de Bezerril
Curvelo, Rebecca Pereira
Cristal, Juqueline Rocha
Carvalho, Augusto Marcelino Pedreira de
Barral, Aldina Maria Prado
Van Weyenbergh, Johan Jozef Rosa Maria
Barral Netto, Manoel
Oliveira, Camila Indiani de
Affilliation: Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação Jose Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative. Salvador, BA, Brasil,
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Salvador, BA, Brasil
Rega Institute for Medical Research. Department of Microbiology and Immunology. KU Leuven, Leuven, Belgium
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Federal University of Bahia. School of Medicine. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil
Abstract: The 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
Keywords: Leishmania braziliensis
Cutaneous leishmaniasis
Genetic
Vaccine
keywords: Leishmania braziliensis
Leishmaniose cutânea
Genética
Vacina
Infecção
Issue Date: 2016
Publisher: Public Library of Science
Citation: Gene 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.
DOI: 10.1371/journal.pntd.0005116
ISSN: 1935-2727
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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