Clinical and immunopathological findings during long term follow-up in Leishmania infantum experimentally infected dogs

Melissa Moura Costa Abbehusen,Leonardo Gil-Santana,Patricia Torres Bozza,Patrícia Sampaio Tavares Veras,Laís Da Silva Pereira,Valter Dos Anjos Almeida,Bruno Bezerril Andrade,Claudia Ida Brodskyn,Deborah Bittencourt Moté Fraga,Washington Luis Conrado Dos-Santos,Manuela Da S Solcà,Dirceu Joaquim Costa

doi:10.1038/s41598-017-15651-8

Abstract

Canine Visceral Leishmaniasis (CVL) is caused by Leishmania infantum, which in the New World is transmitted by Lutzomyia longipalpis. While prospective clinical and immunological assessments of dogs experimentally challenged with L. infantum have been previously reported over a relatively short follow-up period, the long-term characterization of infected animals has not been performed to date. We evaluated dogs in a subclinical state for six years following experimental infection with L. infantum and Lu. longipalpis saliva, via an intradermal route, to characterize clinical, parasitological and immunological parameters arising from L. infantum experimental infection. We also assess these parameters in a group of naturally infected animals. The immune profiles of the experimentally and naturally infected animals exhibited increases of IFN-γ, IL-6 and IL-18, and decreases in TNF, IL-2, IL-8 and CXCL1, compared to controls. Our results indicate that over a six-year follow-up post-challenge, subclinically infected dogs presented low CVL clinical scores despite the persistence of Leishmania parasites in the lymph nodes, spleen and skin. Similarities observed among immune profiles in the context of experimental and natural infection seem to suggest that an enduring activation of the host immune response may lead to the control of parasite growth, thereby limiting disease severity.

Highlights

Canine Visceral Leishmaniasis (CVL) is caused by Leishmania infantum, which in the New World is transmitted by Lutzomyia longipalpis
Considering all the results evaluated at regular intervals throughout the 6-year follow-up period, no significant changes were detected in the observed parameters
In long-term prospective studies conducted in areas endemic for CLV, a limited percentage of naturally infected dogs are observed to become very ill, while the vast majority of animals seem to remain healthy for many years[19,20,21]

Summary

Introduction

Canine Visceral Leishmaniasis (CVL) is caused by Leishmania infantum, which in the New World is transmitted by Lutzomyia longipalpis. We evaluated dogs in a subclinical state for six years following experimental infection with L. infantum and Lu. longipalpis saliva, via an intradermal route, to characterize clinical, parasitological and immunological parameters arising from L. infantum experimental infection. We assess these parameters in a group of naturally infected animals. Dogs are considered the main domestic reservoir of the etiological agent of VL, L. infantum, and canine cases often precede the occurrence of human cases due the close proximity between dogs and humans[2,3,4] This protozoan is mainly transmitted through the bite of infected sand flies, namely Lu. longipalpis in Brazil. A susceptible profile is associated with parasite dissemination and exacerbated proliferation in combination with elevated antibody levels and a suppressed cellular immune response[7,9]

Methods

Results

Conclusion