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

Abstract

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-&#x3b3;). 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-&#x3b3; &#xa0;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-&#x3b3; 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&#x2009;=&#x2009;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&#x2009;=&#x2009;0.044). Regarding IFN-&#x3b3;, all sick dogs demonstrated higher concentrations than healthy dogs (P&#x2009;=&#x2009;0.003). Stage I dogs also exhibited higher IFN-&#x3b3; concentrations compared with healthy dogs (P&#x2009;=&#x2009;0.0002) and with dogs in stage II (P&#x2009;=&#x2009;0.016) and III (P&#x2009;=&#x2009;0.016). Stage II dogs showed higher IFN- &#x3b3; concentrations than healthy dogs (P&#x2009;=&#x2009;0.03). All dogs studied presented a positive correlation between IFN-&#x3b3; and IL-17a concentrations (Spearman's r: 0.54, P&#x2009;<&#x2009;0.0001). Regarding all the sick dogs, a negative correlation was found between IFN-&#x3b3; concentration and antibody levels (Spearman's r: -0.41, P&#x2009;=&#x2009;0.002), and between IL-17a concentration and antibody levels (Spearman's r: -0.27, P&#x2009;=&#x2009;0.044). There was a positive correlation between IFN-&#x3b3; and IL-17a concentration (Spearman's r: 0.61, P&#x2009;<&#x2009;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-&#x3b3;.