Avaliação da deposição de colágeno em lesões de pacientes com leishmaniose tegumentar americana

Abstract

American Tegumentary Leishmaniasis (ATL) is a non-contagious parasitic disease caused by protozoa of the genus Leishmania. Transmission occurs when female sandflies, infected by the parasite, perform hematophagy on a susceptible individual, regurgitating parasites into the dermis. Leishmania then infect cells of the mononuclear phagocytic system, where they multiply causing activation of the immune response. These processes lead to the death of the parasite but also, if not controlled, to cell and extracellular matrix (ECM) destruction, thus resulting in the lesions that characterize the clinical manifestations of the disease. The most frequent clinical form in Brazil is the localized cutaneous (LC), characterized by a single, ulcerated lesion with relatively good therapeutic response. Another form of epidemiological interest is the mucosal manifestation (ML), responsible for destructive lesions, refractory to treatment, commonly associated with relapses. These clinical manifestations are clearly distinct, however the immune response triggered in the tissues of patients with CL and ML share many common characteristics, as well as the criterion of healing being associated with lesion scarring. Considering the clinical, immunological and pathological characteristics of LC and LM, we set out to assess whether collagen deposition and its association with immunological parameters is distinct in the different clinical forms of ATL. For this, biopsies of 16 patients with ACL were collected, 9 with LC and 7 with LM. To quantify the total collagen area, Masson’s Trichrome and Picrosirius Red stains were used. The immunological parameters were obtained from previous studies by our group, in the same lesions analyzed here. Our data showed that there is a significant increase in the area occupied by collagen deposition in the lesions of patients with CL compared to LM. Evaluating the association between collagen deposition and the frequency of subpopulations of CD4+, CD8+, CD68+ cells, or cytokines TNF-α, IFN-γ, IL-10, no significant correlations were observed. However, a negative correlation was observed between collagen expression and the frequency of CD8+ cells expressing the cytotoxic molecule granzyme A, indicating that the greater the area occupied by collagen, the lower the frequency of CD8+granzyme A+ cells. The analysis of principal components and the heat map showed that the analyzes that take into account the measurement of the total area of collagen stratify the LC and LM forms with greater precision, demonstrating that collagen deposition is an important factor in the histopathological differentiation between LC and LM and suggesting that greater collagen deposition is associated with the milder form of ATL. Understanding the mechanisms associated with collagen deposition could open up new strategies to improve healing of ATL lesions.