Interleukin-27 Early Impacts Leishmania infantum Infection in Mice and Correlates with Active Visceral Disease in Humans

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.

Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis

“…For intracellular staining (non-specific cytokine production), splenocytes were cultured for 2h with PMA/Ionomycin (50/500 ng/ml) and then Brefeldin A (10μg/mL) was added for 2 additional hours. Cells were surface stained, fixed and permeabilized with 1% saponin (Sigma-Aldrich, MO, USA) and then intracellularly stained [ 33 ]. Samples were acquired in a FACSCanto (BD) and analyzed with FlowJo software v10 (TreeStar, OR, USA).…”

Interleukin-27 Functional Duality Balances Leishmania Infectivity and Pathogenesis

“…The administration of rIL-27 to in C57BL/6 increases the IL-10 production, while decreasing IFN-γ and IL-12p70 in the peritoneal cavity, and prevents the infiltration of neutrophils in the spleen 24 h after the treatment (102). IL-27 neutralization in acutely infected BALB/c mice reduces parasite burdens and reduces IL-10 levels, while leads to a transient increase in the splenic IFN-γ-producing CD4 + and CD8 + T cells (102). The investigations using EBI3 −/− mice indicate a role for IL-27 in modulating the IL-17 production and neutrophil infiltration during the chronic phase of L. infantum infection (102,103).…”

“…For experimental VL both C57BL/6 and BALB/c strains are considered as susceptible models, but only BALB/c mice, not C57BL/6 mice displayed the augmented serum IL-27 levels during an early stage of L. infantum infection. The phenomenon was attributed to the upregulation of p28 expression by splenic DCs and higher parasite burdens in BALB/c mice (102). High expression of TLR2 by DCs from BALB/c mice may support the early IL-27 expression after infection, which contributes to the attenuating of inflammation and promoting infection (102).…”

“…IL-27 neutralization in acutely infected BALB/c mice reduces parasite burdens and reduces IL-10 levels, while leads to a transient increase in the splenic IFN-γ-producing CD4 + and CD8 + T cells (102). The investigations using EBI3 −/− mice indicate a role for IL-27 in modulating the IL-17 production and neutrophil infiltration during the chronic phase of L. infantum infection (102,103). The EBI3 −/− mice produce considerably higher IL-17A levels than wild-type C57BL/6 mice in both spleen and liver.…”

Development of an Electrochemical Immunosensor for Specific Detection of Visceral Leishmaniasis Using Gold-Modified Screen-Printed Carbon Electrodes

“…Leishmaniasis is a complex of diseases caused by a protozoan of the genus Leishmania [1,2] that affects millions of people worldwide. Visceral leishmaniasis, caused by Leishmania donovani and Leishmania infantum, represents the most severe form and can lead to death if not treated [3,4]. The onset of the infection and clinical manifestations are dependent on many factors including environmental and host immunologic status, especially in the early stages of infection [5].…”