Interleukin‐27 Regulates Adaptative Immune Responses Associated With Control of Parasite Replication in Canine Leishmaniasis

Interleukin 27 (IL‐27) is a cytokine that regulates susceptibility to Leishmania infantum infection in humans and experimental models. This cytokine has not yet been described in canine leishmaniasis (CanL). Therefore, we investigated whether IL‐27 has a regulatory role in CanL. The EBI3 and p28 subunits of IL‐27 were measured in splenic leukocytes culture supernatant from dogs with CanL and compared to control dogs. We also correlated EBI3 and p28 levels with IL‐21, anti‐ L. infantum antibodies and parasite loads. We performed functional assays followed by IL‐27 blockade and measured parasite loads, production of cytokines in splenic leukocytes culture supernatant, and the expression of PD‐1, CTLA‐4, phospho‐Stat‐1/3, T‐bet, GATA3 and nitric oxide production (NO). Both IL‐27 subunits increased in the supernatant of dogs with CanL compared to control dogs. EBI3 and p28 levels showed a moderate positive correlation with IL‐21 ( r = 0.67, p < 0.0001 and r = 0.45, p < 0.012, respectively), and the EBI3 subunit was positively associated with anti‐ L. infantum IgG antibodies ( r = 0.38, p < 0.040) and parasite load ( r = 0.47, p < 0.009). IL‐27 and IL‐21 participate of immune responses in CanL. IL‐27 may be associated with the failure of immunity to control parasite replication via upregulation of the expression of PD‐1, CTLA‐4, T‐bet and NO in splenic leukocytes from dogs with CanL. These findings suggest that the pathways regulated by IL‐27 are involved in CanL pathogenesis in the host, and may be targets for new therapies.