title: Interleukin-27 Early ImpactsLeishmania infantumInfection in Mice and Correlates with Active Visceral Disease in Humans.
abstract: The complexity ofLeishmania-host interactions, one of the main leishmaniasis issues, is yet to be fully understood. We detected elevated IL-27 plasma levels in European patients with active visceral disease caused byLeishmania infantum, which returned to basal levels after successful treatment, suggesting this cytokine as a probable infection mediator. We further addressed this hypothesis recurring to two classical susceptible visceral leishmaniasis mouse models. BALB/c, but not C57BL/6 mice, showed increased IL-27 systemic levels after infection, which was associated with an upregulation of IL-27p28 expression by dendritic cells and higher parasite burdens. Neutralization of IL-27 in acutely infected BALB/c led to decreased parasite burdens and a transient increase in IFN-γ+splenic T cells, while administration of IL-27 to C57BL/6 promoted a local anti-inflammatory cytokine response at the site of infection and increased parasite loads. Overall, we show that, as in humans, BALB/c IL-27 systemic levels are infection dependently upregulated and may favor parasite installation by controlling inflammation.
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Begoña
authors.initials: B
authors.lastname: Pérez-Cabezas
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cecílio
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal.
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Robalo
authors.affiliation: ICVS - Instituto de Investigação em Ciências da Vida e Saúde, Escola de Ciências da Saúde, Universidade do Minho, Braga, Portugal; ICVS/3B's - Laboratório Associado, Braga, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Silvestre
authors.affiliation: WHO Collaborating Centre for Leishmaniasis, Centro Nacional de Microbiología, Instituto de Salud Carlos III , Madrid , Spain.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Carrillo
authors.affiliation: WHO Collaborating Centre for Leishmaniasis, Centro Nacional de Microbiología, Instituto de Salud Carlos III , Madrid , Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Hospital Universitario de Fuenlabrada , Madrid , Spain.
authors.forename: Juan V
authors.initials: JV
authors.lastname: San Martín
authors.affiliation: Departamento de Imunobiologia, Instituto de Biologia, Universidade Federal Fluminense , Niterói , Brazil.
authors.forename: Rita
authors.initials: R
authors.lastname: Vasconcellos
authors.affiliation: i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IBMC - Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal; Faculdade de Farmácia, Departamento de Ciências Biológicas, Universidade do Porto, Porto, Portugal.
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
keywords: IL-27; Leishmania infantum; human; immune regulation; mouse models