, 2003). Additionally, it has been postulated that IL-10 modulates the type 1 immune response in Leishmania-infections by inhibiting IFN-γ production via the suppression of selleck compound IL-12 synthesis in antigen presenting cells ( Lage et al., 2007 and Peruhype-Magalhães et al., 2005). This would imply that the balance between IFN-γ and IL-10 during infection is particularly important in the control of

VL as suggested in an earlier study involving functional models ( Silvestre et al., 2007). In the present study, we have the unique opportunity to perform a compartmentalized characterisation of an immune response in skin from naturally L. chagasi-infected dogs. Since skin is important site to transmission of the infection, the study of the immune response in the skin of dogs infected with L. chagasi and its association with distinct levels of tissue parasitism and clinical progression of CVL will permit new insights elucidating the progressive or protective mechanisms during the infection ( Kemp et al., 1996 and Reis et al., 2009). In the present investigation, dogs showing high skin parasitism exhibited a predominantly immunoregulatory pattern of immune response characterised by increased

expression of IL-10 and TGF-β in comparison with the CD, LP and MP groups (Fig. 2). These findings are consistent with previous reports relating the ability of IL-10 and TGF-β to down-regulate HDAC inhibitor T-cell responses and inhibit the leishmanicidal activity of macrophages

thus leading to the progression of leishmaniasis and/or prevention Maltase of cure (Vouldoukis et al., 1997 and Gantt et al., 2003). Alves et al. (2009) observed that the increased of IL-10 and TGF-β in lymph nodes are correlated with high parasite burden and symptomatic diseases in dogs naturally infected with L. chagasi. Since the experimental animals typically exhibited active CVL, the present results suggest that an increase in IL-10 and TGF-β may lead to the maintenance of parasite multiplication and therefore disease status. Moreover, the IFN-γ/IL-10 (LP: 1845 ± 6138; MP: 1780 ± 4169; HP: 40.58 ± 128.2) and IL-12/IL-10 (LP: 69.95 ± 85.06; MP: 90.80 ± 97.24; HP: 16.13 ± 31.06) ratios were lower in the HP group than in the other groups (p < 0.05). Accordingly, LP showed a significant increase in IL-12 expression in comparison HP and a negative correlation was observed between IL-12 levels and increase of skin parasite density ( Fig. 2). Additionally, the data revealed that increases in IL-12 were negatively correlated with the levels of the immunoregulatory cytokines IL-10 and TGF-β1 ( Fig. 3). The results presented here thus re-emphasise the involvement of immunoregulatory cytokines in the suppression of the immune response involved in the control of parasite replication in the skin.