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

Pérez-Cabezas, Begoña; Cecílio, Pedro; Robalo, Ana Luisa; Silvestre, Ricardo; Carrillo, Eugenia; Moreno, Javier; Martín, Juan San; Vasconcellos, Ricardo José de Holanda; Cordeiro-da-Silva, Anabela

doi:10.3389/fimmu.2016.00478

Cited by 14 publications

(18 citation statements)

References 34 publications

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“…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).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the “natural infection”.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2017

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“…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).…”

Section: Il-27 Modulates Il-17 To Affect Neutrophil Infiltration In Tmentioning

confidence: 99%

“…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).…”

Section: Il-27 Is a Regulatory Cytokine That Dictates Susceptibility mentioning

confidence: 99%

“…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.…”

Section: Il-27 Modulates Il-17 To Affect Neutrophil Infiltration In Tmentioning

confidence: 99%

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Interleukin-27 Functional Duality Balances Leishmania Infectivity and Pathogenesis

et al. 2020

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IL-27 is a cytokine that exerts diverse effects on the cells of innate and adaptive immune systems. Chiefly expressed in macrophages and dendritic cells during the early phase of Leishmania infection, IL-27 contributes to the protection against L. major infection but suppresses the protective Th1 response against L. donovani, L. infantum, L. amazonensis and L. braziliensis infections, suggesting its functional duality. During the late stage of Leishmania infection, IL-27 limits the immunopathogenic reactions and tissue damages. Herein, we analyze the mechanism of the functional duality of IL-27 in the resistance or susceptibility to Leishmania infection, prompting IL-27 for anti-Leishmanial therapy.

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“…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].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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Visceral leishmaniasis is a reemerging neglected tropical disease with limitations for its diagnosis, including low concentration of antibodies in the serum of asymptomatic patients and cross-reactions. In this context, this work proposes an electrochemical immunosensor for the diagnosis of visceral leishmaniasis in a more sensitive way that is capable of avoiding cross-reaction with Chagas disease (CD). Crude Leishmania infantum antigens tested in the enzyme-linked immunosorbent assay (ELISA) were methodologically standardized to best engage to the sensor. The antibodies anti-Trypanosoma cruzi and anti-Leishmania sp. Present in serum from patients with diverse types of CD or leishmaniasis were chosen. A screen-printed carbon electrode modified with gold nanoparticles was the best platform to guarantee effective adsorption of all antigens so that the epitope of specific recognition for leishmaniasis occurred efficiently and without cross-reaction with the evaluated CD. The current peaks reduced linearly after the recognition, and still were able to notice the discrimination between different kinds of diseases (digestive, cardiac, undetermined Chagas/acute and visceral chronic leishmaniasis). Comparative analyses with ELISA were performed with the same groups, and a low specificity (44%) was verified due to cross-reactions (high number of false positives) on ELISA tests, while the proposed immunosensor presented high selectivity and specificity (100%) without any false positives or false negatives for the serum samples from isolated patients with different types of CD and visceral leishmaniasis. Furthermore, the biosensor was stable for 5 days and presented a detection limit of 200 ng mL−1.

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

Cited by 14 publications

References 34 publications

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

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

Interleukin-27 Functional Duality Balances Leishmania Infectivity and Pathogenesis

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

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