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

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.