title: Gene Expression Profile of High IFN-γ Producers Stimulated with Leishmania braziliensis Identifies Genes Associated with Cutaneous Leishmaniasis.
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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.
authors.forename: Marcia W
authors.initials: MW
authors.lastname: Carneiro
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.
authors.forename: Kiyoshi F
authors.initials: KF
authors.lastname: Fukutani
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.|Multinational Organization Network Sponsoring Translational and Epidemiological Research (MONSTER) Initiative, Fundação José Silveira, Salvador, Brazil.
authors.forename: Bruno B
authors.initials: BB
authors.lastname: Andrade
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Curvelo
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.
authors.forename: Juqueline R
authors.initials: JR
authors.lastname: Cristal
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.
authors.forename: Augusto M
authors.initials: AM
authors.lastname: Carvalho
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.|Federal University of Bahia School of Medicine, Salvador, Brazil.
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.affiliation: Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Van Weyenbergh
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.|Federal University of Bahia School of Medicine, Salvador, Brazil.
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
authors.affiliation: Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil.
authors.forename: Camila I
authors.identifier: 0000-0002-7868-5164
authors.initials: CI
authors.lastname: de Oliveira
mesh_terms: D000818:Animals; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D053614:Janus Kinase 2 / Q000235:genetics / Q000276:immunology; D007892:Leishmania braziliensis / Q000235:genetics / Q000502:physiology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology; D059467:Transcriptome
chemical_list: C406887:IFI27 protein, human; D015850:Interleukin-6; D008565:Membrane Proteins; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D007371:Interferon-gamma; C507924:JAK2 protein, human; D053614:Janus Kinase 2