Extracellular matrix alterations in experimental Leishmania amazonensis infection in susceptible and resistant mice

Leishmaniasis represents a complex of diseases with important clinical and epidemiological diversity. Clinical forms of leishmaniasis are particularly diverse: visceral leishmaniasis (VL) is usually fatal when untreated, mucosal leishmaniasis (ML) is a mutilating disease, diffuse cutaneous leishmaniasis (DCL) is a long-lasting disease due to a deficient cellular-mediated immune response and cutaneous leishmaniasis (CL) is disabling when lesions are multiple [1]. Infected sandflies deposit Leishmania promastigotes within the host skin, after that the parasite is taken up into a membrane bound phagosome that is contiguous with the outer plasma membrane of the macrophage; hence, the parasite is initially in the extracellular environment [2].The extracellular matrix is composed of a wide variety of different macromolecules which carry distinct domains with defined structural and/or biological activities. Cell-matrix interactions, therefore, not only control the shape and orientation of cells but can also directly or indirectly regulate cellular functions, including migration, differentiation, proliferation and the expression of different genes [3].A copious elastic-fibre network is responsible for skin elasticity. These fibres extend from the dermal-epidermal junction as cascades of microfibril bundles (oxytalan fibres), through perpendicular elaunin fibres in the papillary dermis that contains small amounts of elastin, to thick horizontally aligned elastic fibres in the reticular dermis [4]. Collagen fibres, which are formed by a superfamily of 27 members divided into subgroups, provide tensile strength to the skin. At least three characteristics determine a collagen: the localization, always extracellular; the presence of at least one triple helix in its structure; and the ability to form macromolecular aggregates. These fibres are secreted by different cells, mostly from connective tissue, and represent 25% of the whole-body protein content of mammals [5].Studies hav