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In Leishmania donovani infection, lesions are randomly distributed in the skin. However, some preferential sites (e.g. ears, nose, and paws) have been described. In this study, the relationship between host and parasite factors that predispose the skin to L donovani are investigated. The results demonstrate that in the snout of L donovani-infected mice, the cells of the dendritic cell-macrophage lineage are the prevalent cells, which constitute the epithelium and dermis. Furthermore, an increase in the expression of tumor necrosis factor-alpha (TNF-alpha) occurs in the majority of sensitized mice. This increase is associated with the pathogenicity of L donovani, as evidenced by the increase in the number of lesions, the size of the lesions, the higher production of nitric oxide (NO), and the decrease in the number of CD4(+) lymphocytes, but without modification of the expression of 0b46394aab