Identification of immunogenic peptides of Fonsecaea pedrosoi and its possible use as vaccine in the experimental chromoblastomycosis

Abstract

Chromoblastomycosis is a chronic subcutaneous fungal infection acquired by traumatic means, through the penetration of conidia and fragments of hyphae of the fungus by the solution of the skin continuity. Most of the reported cases of chromoblastomycosis have as etiological agent F. pedrosoi and mainly affect the countries of tropical and subtropical regions. In Brazil, the disease has been described in almost all states, with the main foci being the states of the Amazon region, São Paulo, Rio de Janeiro, Minas Gerais and Rio Grande do Sul. Treatment of chromoblastomycosis is a therapeutic challenge, so that although several methods and antimicrobials are used in attempts to cure or control the disease, there are many cases of relapses and few reports of definitive cure, and there is still no effective therapeutic standard in the fight against this infection. We believe that an isolated specific therapy does not act on the cellular immune response and the treatment administered is not effective, mainly due to the appearance of frequent relapses. We suggest that immunotherapy may be a key to assist in the treatment of patients with chromoblastomycosis, especially those who do not respond to a conventional therapy currently administered. APCs (Antigen Presenting Cells), such as macrophages and dendritic cells, are able to recognize and phagocyte the fungus. In order for recognition by host cells to occur, the PAMPs (pathogen associated pathogens) expressed on the fungus surface must be recognized by the PRRs (standard recognition receptors) located on the surface of the APCs, generating a series of reactions , such as phagocytosis of the fungus. After phagocytosis the immunogenic peptides of the fungus are processed by phagocytes and presented to the T lymphocytes, generating effector cells and memory cells against the pathogen. The antigen presentation occurs through the class I MHC (Class I major histocompatibility complex) and the MHC class II lymphocytes that predominate TCD8 + and TCD4 + lymphocytes, respectively. After activation, TCD4 + cells differentiate into Th1, Th2, Th17 (T lymphocytes helper) or Treg (regulatory lymphocytes) with production of different cytokines, generating different types of responses (WÜTHRICH et al., 2012). Recent data obtained by our group showed that the absence of IFN-³-producing T cells induces a severe infection by F. pedrosoi, suggesting that the presence of these cells and the Th1 response is essential for assembling a protective response in the hostKnowing the importance of the adaptive response in fungal infections, and of possible biological mediators that stimulate this response, this work aims to map the immunogenic peptides through the immunoreactive proteins of the fungus Fensecaea pedrosoi, and evaluate them as regards the protective character in murine experimental chromoblastomycosis