Mixed cytokine profile during active cutaneous leishmaniasis and in natural resistance

Most studies on immune response in human cutaneous leishmaniasis evaluate patients with active disease in comparison with healthy uninfected controls or patients that have had the lesions healed, however, little is known about the immune response associated with natural resistance. In this paper we evaluate the cytokine expression patterns of T-cells and the plasmatic levels of nitrite and nitrate in patients with localized cutaneous leishmaniasis (LCL) as well as endemic non-infected individuals with positive (MST) and negative (NI) Montenegro skin test, without previous history of leishmanial lesions. Our results demonstrated an increased number of IFN-gamma(+) and TNF-alpha(+) T-cells and high level of plasma nitrite and nitrate in LCL patients. Moreover, we have observed that early in infection (LCL equal/less than 60 days of lesion evolution), Leishmania patients present predominance in IL-4(+) and IL-10(+) T-lymphocytes. However, this is a transitory phenomenon, since patients with older lesions (LCL more than 60 days of lesion evolution) show a predominant Type-1 immune profile, suggesting that disease development may depend on a transient deregulation of T-cell response, during the initial phase of infection. Interestingly MST displayed a basal mixed Type-0 cytokines profile. However, the low frequency of IL-4(+) T-cells, high IFN-gamma(+)/IL-10(+) cell ratio as well as elevated nitrite and nitrate plasma levels observed in MST, suggested that despite basal levels of cytokines, a high proportion of Type-1 over Type-2 cytokines would count to prevent parasite growth and lesion development.