Association of Pro-Inflammatory Cytokines and Iron Regulatory Protein 2 (IRP2) with Leishmania Burden in Canine Visceral Leishmaniasis

Paulo Ricardo Porfírio Do Nascimento,Ádila Lorena Morais Lima,Francisco Paulo Freire-Neto,Paula Vivianne Queiroz,Daniella Regina Arantes Martins,Selma Maria Bezerra Jeronimo,Glória Regina Góis Monteiro,José Wilton Queiroz,Kelly A Brayton

doi:10.1371/journal.pone.0073873

Abstract

Leishmania infantum infection in humans and dogs can evolve with a wide range of clinical presentations, varying from asymptomatic infections to visceral leishmaniasis. We hypothesized that the immune response elicited by L. infantum infection could modulate whether the host will remain asymptomatic or progress to disease. A total of 44 dogs naturally infected with L. infantum were studied. Leishmania burden was estimated in the blood and spleen by qPCR. The expression of IFN-γ, TNF-α, IL-10 and Iron Regulatory Protein 2 (IRP2) were determined in the spleen by quantitative PCR. Sera cytokines were evaluated by ELISA. Dogs were grouped in quartiles according parasite burden. Increased expression of IFN-γ and TNF-α was associated with reduced Leishmania burden, whereas increased IL-10 and IRP2 expressions were associated with higher Leishmania load. Increased plasma albumin and IFN-γ expression explained 22.8% of the decrease in parasite burden in the spleen. These data confirm that lower IFN-γ response and higher IL-10 correlated with increased parasite load and severity of the visceral leishmaniasis in dogs. The balance between the branches of immune response and the intracellular iron availability could determine, in part, the course of Leishmania infection.

Highlights

Leishmania infantum infection can result in a wide range of clinical outcomes, varying from self-resolving infection to visceral leishmaniasis, which can be fatal, even with treatment [1]
L. infantum infection causes a wide range of clinical outcomes in humans and dogs which are associated with several factors including the host immune responses, parasite polymorphisms, exposure to the sand fly vectors, and coinfections [25,26]
Leishmania load was lower in the blood than in the spleen, corroborating findings by Teixeira Neto et al [27], which showed increase parasitism with the severity of the Leishmania infection

Summary

Introduction

Leishmania infantum infection can result in a wide range of clinical outcomes, varying from self-resolving infection to visceral leishmaniasis, which can be fatal, even with treatment [1]. In the last 20 years VL became a disease of perimetropolitan areas of major cities in Brazil [3,4,5,6] and has spread to other countries in Latin America [7]. These changes have resulted in a large population at risk of L. infantum infection. Children with symptomatic VL in Bangladesh had lower serum levels of retinol and zinc compared to uninfected and asymptomatically infected people [12]

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Conclusion