LAUSR

Cutaneous Leishmaniasis (CL) is considered a neglected disease, mainly linked to low socioeconomic conditions (1, 2). Currently, estimates suggest 900,000 to 1.5 million new cases per year with 95% of the cases in the Americas, Mediterranean and Asia (3). The disease clinical manifestation can range from a single to multiple lesions, being observed in 90% of cases a nodular ulcerative squamous lesion. After inoculation of the metacyclic promastigote of Leishmania into the host skin by the sandfly bite, a papule forms at the site of bite, and later it turns into an ulcerated lesion with delineated borders, a reddish background, and an intense inflammatory infiltration (lymphocytes, phagocytes, and plasma cells) (4–9).. Factors such as the species of Leishmania involved in the infection and the host immune response directly influence the lesion type and clinical outcome in the patient (10, 11). After dermis inoculation the promastigotes cause activation of the complement system and factor C3b deposition on the parasite surface. However it has been demonstrated that Leishmania protease GP63 is able to inactivate C3b (12). These promastigotes are opsonized, by the C3 molecule of the complement system, to be phagocytized by phagocytic immune cells. Among these phagocytic cells are neutrophils, dendritic cells, and macrophages (13–15). Neutrophils are the first cells to arrive at the infection site, being attracted by complement proteins, cytokines (e.g., IL-8), and chemokines (e.g., CXCL1 and CXCL2). These cells can eliminate the parasites through the action of nitric oxide (NO) and other reactive oxygen species (ROS), and also produce high levels of chemokines such as CXCL8 and CXCL9, responsible for the recruitment of more neutrophils and Th1 cells (16–18). In addition, because they are short-lived phagocytic cells, they promote the entry of more promastigotes in macrophages phagocyting dead neutrophils. Thus, neutrophils serve as a “trojan horses”, but the macrophages also produce cytokines which will in turn activate other immune cells (19, 20). Resident dendritic cells (DCs) seems to play a key role in the immunopathogenesis of CL (21, 22). Once these cells interact with Leishmania there is an increase in the expression of costimulatory molecules, such as CD40, CD80 and CD86 which are essential for T cell activation (23, 24). Thus, it is hypothesized that resident DCs recruit monocytes, which differentiate into monocyte-derived dendritic cells (moDCs). These cells have an intense phagocytic activity, and evidences suggests that they favor the growth and survival of parasites (25, 26).