AUTHOR=Pérez-Cabezas Begoña , Cecílio Pedro , Robalo Ana Luisa , Silvestre Ricardo , Carrillo Eugenia , Moreno Javier , San Martín Juan V. , Vasconcellos Rita , Cordeiro-da-Silva Anabela TITLE=Interleukin-27 Early Impacts Leishmania infantum Infection in Mice and Correlates with Active Visceral Disease in Humans JOURNAL=Frontiers in Immunology VOLUME=7 YEAR=2016 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2016.00478 DOI=10.3389/fimmu.2016.00478 ISSN=1664-3224 ABSTRACT=

The complexity of Leishmania–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 by Leishmania 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.