In addition, tissue-infiltrating IL-17+ cells co-expressed CCR6 (Fig. 2L), a chemokine receptor known to be present in neutrophils and Th17 cells and related to the migration of these cells to inflamed tissues. CCR6+ cells producing IL-17 within the lesion site corroborate the hypothesis that Th17 migration is mediated by this chemokine receptor 18. Because Th17-driven inflammation is classically characterised by neutrophil infiltration 19, we investigated the presence of these cells in ML lesions. Neutrophils were observed in all ML lesions with varying frequency

between patients. Neutrophils were concentrated mainly in the epithelium and lamina propria, at the edges of ulcerous or necrotic areas (36±26 cells/mm2, Fig. 3A and H). Their density was much lower in the deeper portions of the chronic see more inflammatory infiltrate, where Ganetespib in vitro only a few isolated neutrophils were observed (4±8 cells/mm2, Fig. 3H). Superficial erosions are frequently detected in this area during clinical examination of ML patients, which may be related to neutrophil infiltration and expression of proteinases. In 30% of ML specimens, large numbers of neutrophils were observed inside dilated capillaries only. In two patients, neutrophil aggregates were observed in intraepithelial pustules (Fig. 3B and D). Moreover,

neutrophils exhibited intense immunostaining for neutrophil elastase (NE; Fig. 3C and Niclosamide E), myeloperoxidase (MPO; Fig. 3D and F) and MMP9 (Fig. 3G). Assuming that Th17 cells mediate neutrophil infiltration in ML lesions, IL-17 may favour inflammatory immune responses in ML patients by recruiting neutrophils. In experimental cutaneous leishmaniasis, lesion progression is related to IL-17-mediated neutrophil recruitment,

whereas improved disease outcome is associated with decreased neutrophil immigration in IL-17-deficient mice 8. However, neutrophils contribute to parasite clearance in the early steps of experimental leishmania infection 19 and activate macrophages to kill L. major by a mechanism that requires NE 20. Thus, the presence of neutrophils in this inflammatory context can be indicative of either protection or injury. Taken together, the data presented here demonstrate that Th17 conditions, as well as CD8+ and CD14+ cells expressing IL-17, participate in the inflammatory response to ML. Neutrophil chemotaxis with proteinase release in ML lesions in damaged areas can be mediated by Th17 cells. Investigating the role of Th17 cells in ML may lead to new strategies of enhancing protective immunity and minimising immune response-mediated tissue damage during this disease. Tissue samples were obtained from 17 ML patients (1.4 male/female ratio, aged 59±17 years) at our field clinic in the Bahia State, Brazil.