Background Leishmania infantum infection progression in dogs depends on the interaction between the parasite and the host’s immune response. The adaptive immune response, primarily mediated by T-helper 1 lymphocytes, promotes an effective reaction by increasing cytokines such as interferon-gamma (IFN-γ). In addition, interleukin-17a (IL-17a) plays a role in controlling parasite growth through inducible nitric oxide synthase activation. However, limited data exist on IL-17a production in dogs at different disease stages. This study aimed to evaluate L. infantum-specific IL-17a production in blood samples from dogs with varying clinical stages of leishmaniosis and to assess its correlation with disease severity, humoral response, and IFN-γ  concentrations. Methods In total, 65 dogs were included; 10 healthy seronegative and 55 sick dogs, classified into three groups according to the LeishVet clinical stages, were studied. IFN-γ and IL-17a concentrations were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) after performing a L. infantum-specific cytokine release whole-blood assay following stimulation with soluble L. infantum antigen. Results No significant differences in IL-17a concentration were observed between healthy and all sick dogs (P = 0.77). Dogs in stage I presented higher IL-17a concentrations than dogs in stages II and III. However, the difference was only statistically significant when compared with stage III (P = 0.044). Regarding IFN-γ, all sick dogs demonstrated higher concentrations than healthy dogs (P = 0.003). Stage I dogs also exhibited higher IFN-γ concentrations compared with healthy dogs (P = 0.0002) and with dogs in stage II (P = 0.016) and III (P = 0.016). Stage II dogs showed higher IFN- γ concentrations than healthy dogs (P = 0.03). All dogs studied presented a positive correlation between IFN-γ and IL-17a concentrations (Spearman’s r: 0.54, P < 0.0001). Regarding all the sick dogs, a negative correlation was found between IFN-γ concentration and antibody levels (Spearman’s r: −0.41, P = 0.002), and between IL-17a concentration and antibody levels (Spearman’s r: −0.27, P = 0.044). There was a positive correlation between IFN-γ and IL-17a concentration (Spearman’s r: 0.61, P < 0.0001). Conclusions This study demonstrates that IL-17a production is increased in mild disease when compared with more advanced clinical stages, acting as a possible “resistance” marker. However, IL-17a seems to be less reliable as a marker when compared with IFN-γ. Graphical Abstract

Leishmania infantum-specific production of IL-17a in stimulated blood from dogs in different clinical stages of leishmaniosis

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2025年11月27日

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Icíar Martínez-Flórez,
Marta Baxarias,
Laia Solano-Gallego

摘要

Background

Leishmania infantum infection progression in dogs depends on the interaction between the parasite and the host’s immune response. The adaptive immune response, primarily mediated by T-helper 1 lymphocytes, promotes an effective reaction by increasing cytokines such as interferon-gamma (IFN-γ). In addition, interleukin-17a (IL-17a) plays a role in controlling parasite growth through inducible nitric oxide synthase activation. However, limited data exist on IL-17a production in dogs at different disease stages. This study aimed to evaluate L. infantum-specific IL-17a production in blood samples from dogs with varying clinical stages of leishmaniosis and to assess its correlation with disease severity, humoral response, and IFN-γ concentrations.

Methods

In total, 65 dogs were included; 10 healthy seronegative and 55 sick dogs, classified into three groups according to the LeishVet clinical stages, were studied. IFN-γ and IL-17a concentrations were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) after performing a L. infantum-specific cytokine release whole-blood assay following stimulation with soluble L. infantum antigen.

Results

No significant differences in IL-17a concentration were observed between healthy and all sick dogs (P = 0.77). Dogs in stage I presented higher IL-17a concentrations than dogs in stages II and III. However, the difference was only statistically significant when compared with stage III (P = 0.044). Regarding IFN-γ, all sick dogs demonstrated higher concentrations than healthy dogs (P = 0.003). Stage I dogs also exhibited higher IFN-γ concentrations compared with healthy dogs (P = 0.0002) and with dogs in stage II (P = 0.016) and III (P = 0.016). Stage II dogs showed higher IFN- γ concentrations than healthy dogs (P = 0.03).

All dogs studied presented a positive correlation between IFN-γ and IL-17a concentrations (Spearman’s r: 0.54, P < 0.0001). Regarding all the sick dogs, a negative correlation was found between IFN-γ concentration and antibody levels (Spearman’s r: −0.41, P = 0.002), and between IL-17a concentration and antibody levels (Spearman’s r: −0.27, P = 0.044). There was a positive correlation between IFN-γ and IL-17a concentration (Spearman’s r: 0.61, P < 0.0001).

Conclusions

This study demonstrates that IL-17a production is increased in mild disease when compared with more advanced clinical stages, acting as a possible “resistance” marker. However, IL-17a seems to be less reliable as a marker when compared with IFN-γ.

Graphical Abstract