Cytokine gene expression in feline leishmaniasis: why cats might be less clinically affected than dogs.

Abstract

BACKGROUND: Canine leishmaniasis caused by Leishmania infantum is recognized as one of the most important neglected vector-borne diseases of zoonotic concern worldwide. Cats may also be infected with L. infantum, though the mechanisms underlying the immune response to this protozoal infection in the feline host remain poorly understood. In this study, the early cytokine gene-expression profile was investigated by in vitro infection of feline monocyte-derived macrophages with L. infantum. METHODS: Primary macrophages were matured from peripheral blood mononuclear cells of a healthy domestic cat, and cells were collected at different time points post-infection (i.e., 4, 24, and 72 h) for microscopic evaluation and quantitative real-time PCR analysis of cytokine expression [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α]. RESULTS: Infection rates ranged from 35.6% to 48.2%, with 2.1-2.4 intracellular parasites per infected cell. Gene-expression analysis revealed a marked upregulation of IL-2, IFN-γ, and TNF-α at 72 h, indicating a predominant Th1-type pro-inflammatory response, while IL-4, IL-6, and IL-10 remained stable or slightly downregulated. CONCLUSIONS: These findings provide unprecedented evidence that feline macrophages activate a Th1-like cytokine pattern following in vitro infection with L. infantum. Overall, the outcomes of this investigation support the hypothesis that, when compared with dogs, the milder clinical course of leishmaniasis in cats is related to a predominant Th1-like immune response, eventually contributing to the infection control in naturally infected animals.