DH82 Canine and RAW264.7 Murine Macrophage Cell Lines Display Distinct Activation Profiles Upon Interaction With Leishmania infantum and Leishmania amazonensis

Leishmaniasis is an anthropozoonotic disease and dogs are considered the main urban reservoir of the parasite. Macrophages, the target-cell of Leishmania sp., play an important role during infection. Although dogs have a major importance in the epidemiology of the disease, the majority of the current knowledge about Leishmania-macrophage interaction comes from murine experimental models. To assess whether the canine macrophage strain DH82 is an accurate model for the study of Leishmania interaction, we compared its infection by two species of Leishmania (Leishmania infantum and L. amazonensis) with the murine macrophages cell line (RAW264.7). Our results demonstrated that L. amazonensis survival was around 40% at 24 h of infection inside both macrophages cell lines, however, it was observed a reduction of 4.3 times in L amazonensis infection at 48 h post infection in RAW 264.7 macrophages. The survival index of L. infantum in DH82 canine macrophages was around 3 times higher than in RAW264.7 murine cells at 24 and 48 h post infection, however in 48 h a reduction in both macrophages is observed. Surprisingly at 24 h post infection, NO and ROS production by DH82 canine cells stimulated with LPS or menadione or during Leishmania infection was minor compared to murine RAW264.7 However basal arginase activity was higher in DH82 cells when compared to murine RAW264.7 cells. Analysis of the cytokines showed that these macrophages present a different response profile. L infantum induced IL-12 and L. amazonensis induce IL-10 in both cell lines. However L infantum and L. amazonensis also induced TGF-β in RAW 264.7. CD86 and MHC expression showed that L. amazonensis modulate them in both cell lines. Conversely, the parasite load profile did not show significant difference between both macrophages cell lines after 48 h of infection, which suggest that other mechanism of Leishmania control, could be involved in DH82 cells.