Characterization of histopathological changes and cellular immune response in cutaneous lesions of patients with cutaneous leishmaniosis in Panama

Author(s)

Kadir Amilcar Gonzalez Carrion

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2020-10-28

Examining board members

Marcia Dalastra Laurenti; Claudia Maria de Castro Gomes; Hiro Goto; Azael Saldaña Partiño

• Advisor: Marcia Dalastra Laurenti

Abstract

Leishmaniasis is considered a spectral disease with multiple clinical and immunopathological characteristics in humans, depending on the host\'s immunogenic characteristics and parasite species. In Panama, the most prevalent species of the parasite is Leishmania (Viannia) panamensis, which causes Cutaneous Leishmaniasis (LC), the most prevalent zoonosis in the country. The few knowledges about the pathogenesis of the disease caused by this species, in addition to the increased incidence of human cases observed in many regions of America, led us to study the immunopathological aspects of the skin lesion caused by this species of the parasite in Panama. Thus, the main objective of this study was to characterize the cellular, inflammatory and regulatory immune response and the histopathological aspects of skin lesions in LC in Panamanian patients (n = 46) using histological sections stained by HE and processed by immunohistochemistry (IHC). Infection with L. (V.) panamensis was confirmed by the isolation and characterization of the parasites by HSP70-RFLP. Immunohistochemistry has proved to be a complementary tool for diagnosis, improving the sensitivity of histopathological analysis to find amastigote forms of the parasite. The histopathological changes observed were characterized by a moderate inflammatory reaction in the dermis with focal predominance with patterns of presentation lympho-histiocytic, lympho-plasmacytic and granulomatous; and presence of ulcers, acanthosis, exocytosis and spongiosis in the epidermis, in agreement with the histopathological patterns observed by the species causing the localized form of LC of the subgenus Viannia. The cellular immune response was characterized by the predominance of T cells producing IFN-y and IL-10 (CD4 and CD8) and IL-13 (CD4). The participation of CD8 may be related to tissue damage due to the production of granzyme B. In addition, we observed the participation of Th17 cellular immune response and markers that characterize the presence of the inflammasome, which can contribute to the elimination of the parasite, however its contribution to the maintenance of the inflammatory process cannot be ruled out. T-regulatory response mainly associated with the production of IL-10, controlling the exacerbated inflammatory response, was also present. These results show a mixed cellular immune response in the localized skin lesions caused by L. (V.) panamensis. The results obtained contribute to the knowledge of the pathogenesis of human infection caused by L. (V.) panamensis and can assist in future studies on therapeutic schemes and development of vaccines, contributing to the control programs of this important neglected disease (AU)

• FAPESP's process: 17/03141-5 - Characterization of histopathological changes and cellular immune response in cutaneous lesions of patients with Tegumentary Leishmaniasis in Panamá
• Grantee: Kadir Amilcar Gonzalez Carrion
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)