Leishmaniasis is endemic in several parts of the world, with a global prevalence of over 12 million cases and 1.5–2 million new cases emerging every year [
1]. The infection is caused by protozoan parasites of the genus
Leishmania, transmitted through the bite of the sand fly vector. Several
Leishmania species are able to cause a wide spectrum of clinical manifestations, ranging from the mild cutaneous form, the disfiguring mucosal form and the life-threatening visceral form, also known as kala-azar. In Brazil,
Leishmania (L.) braziliensis causes cutaneous and mucosal disease,
L. amazonensis causes cutaneous and, sporadically, visceral disease, while
L. chagasi is exclusively associated with visceral disease. The clinical outcome of infection thus not only depends on the species involved, but also on the patient's immunocompetence. In recent years, a protective immune response against intracellular pathogens, such as
Leishmania, Listeria and mycobacteria, has been defined as type 1 (Th1), whereas protection against extracellular pathogens, such as helminths, requires a type 2 (Th2) response. The murine model of experimental leishmaniasis has been instrumental for the elaboration of the Th1/Th2 paradigm, inasmuch as the preferential action of Th1 (IFN-γ, IL-12, TNF-α) or Th2 cytokines (IL-4, IL-5, IL-10) results in cure or progression of the disease, respectively [
2,
3]. In human leishmaniasis, this Th1/Th2 dichotomy is much less explicit for in vitro or ex vivo cytokine production. However, striking differences in cellular (lymphoproliferation and IFN-γ production) and humoral (total and anti-
Leishmania IgG) immune response can be observed in different clinical forms of the disease. Our group has recently shown that patients with localized cutaneous leishmaniasis (LCL) display a diminished Th1 response during the early phase of disease, which is reverted after treatment [
4]. In mucosal leishmaniasis (ML), on the other hand, an exacerbated Th1 response with increased IFN-γ and TNF-α levels, is believed to provoke tissue destruction [
5]. In patients with visceral leishmaniasis (VL), characterized by immunosuppression and absence of IFN-γ production [
6], we were able to show the beneficial effect IFN-γ
in vivo [
7]. Although zinc deficiency has been shown to lead to a selective Th1 deficiency in human volunteers [
8], only few data are available on the role of trace elements in human leishmaniasis, being restricted to Old World LCL, showing increased serum copper and decreased serum zinc in Turkish LCL patients infected by
L. major [
9]. In this study, we investigated if Zn and Cu levels differ in different clinical forms of the disease, and if these trace metals might be correlated to anti-parasite immune response.