Role of CD4+CD25+FoxP3+ Regulatory T cells in the post-infection and post-vaccination immune response to Sporothrix schenckii

• Grant number: 16/04250-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2016
• End date: October 31, 2020
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Iracilda Zeppone Carlos
• Grantee: Alexander Batista Duharte
• Host Institution: Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Associated scholarship(s): 18/15187-2 - Effect of Foxp3 silencing on immunogenicity of vaccines against Sporothrix schenckii, BE.EP.PD

Abstract

Sporotrichosis is a worldwide distributed subcutaneous mycosis, mainly in tropical and subtropical countries, and it is considered to be emerging in Brazil and other countries. The causative agents are species from the Sporothrix schenckii complex that live in the soil. Among the species of the complex, S. schenckii sensu strictu is the causative agent present in all countries, whereas S. brasiliensis is specifically found in Brazil, where this infection is already considered an important zoonosis. The immune mechanisms involved in preventing and controlling the disease are not completely understood. One of the risk factors that determine the susceptibility to disease severity is the immune status of the host. In fact, the disease is more severe and often disseminated in nude mice and AIDS patients, suggesting the T cell-mediated immunity is of great importance against this infection. Studies in our laboratory demonstrated the role of innate immunity and of different T lymphocyte populations, including Th1, Th2 and Th17, in the immune response against S. schenckii in infection models and during response to a specific vaccine candidate. Regulatory T (Treg) cells are a fundamental lymphocyte population for controlling immunity and the excessive tissue damage caused in response to different infections, including those by fungi. However, so far there are no studies of its influence in controlling the immune response to the S. schenckii infection and of how they would participate during the induction phase of the immune response after vaccination against the fungus. Thus, we propose a comprehensive assessment of the role of CD4+CD25+Foxp3+ Treg cells in infection by S. schenckii, from their frequency during infection by this pathogen to the assessment of their activity and relevance to the post-infection and post-vaccination immune response in Treg-depleted or non-depleted transgenic DEREG (DEpletion of REGulatory T cells) mice. The obtained results will aid the better understanding of the role of Treg cells during fungal infections and in the course of post-vaccination responses, besides supporting development of immunomodulatory strategies for the prophylaxis and treatment of sporotrichosis, which is especially important for immunocompromised patients. (AU)

Scientific publications

(5)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BATISTA-DUHARTE, ALEXANDER; TELLEZ-MARTINEZ, DAMIANA; PORTUONDO FUENTES, DEIVYS LEANDRO; CARLOS, IRACILDA ZEPPONE. Molecular adjuvants that modulate regulatory T cell function in vaccination: A critical appraisal. PHARMACOLOGICAL RESEARCH, v. 129, p. 237-250, MAR 2018. (16/04250-0)

TELLEZ-MARTINEZ, DAMIANA; BATISTA-DUHARTE, ALEXANDER; PORTUONDO, DEIVYS LEANDRO; CARLOS, IRACILDA ZEPPONE. Prophylactic and therapeutic vaccines against sporotrichosis. Feasibility and prospects. Microbes and Infection, v. 21, n. 10, p. 432-440, DEC 2019. (17/26774-3, 16/04250-0)

BATISTA-DUHARTE, ALEXANDER; TELLEZ-MARTINEZ, DAMIANA; PORTUONDO, DEIVYS LEANDRO; CARLOS, IRACILDA ZEPPONE. Selective depletion of regulatory T cells enhances the immunogenicity of a recombinant-based vaccine against Sporothrix spp. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, v. 12, p. 9-pg., 2023-02-10. (21/05494-8, 16/04250-0)

BATISTA-DUHARTE, ALEXANDER; TELLEZ-MARTINEZ, DAMIANA; DE ANDRADE, CLEVERTON ROBERTO; PORTUONDO, DEIVYS LEANDRO; JELLMAYER, JULIANA APARECIDA; POLESI, MARISA CAMPOS; CARLOS, IRACILDA ZEPPONE. Sporothrix brasiliensis induces a more severe disease associated with sustained Th17 and regulatory T cells responses than Sporothrix schenckii sensu stricto in mice. FUNGAL BIOLOGY, v. 122, n. 12, p. 1163-1170, DEC 2018. (16/04250-0)

BATISTA-DUHARTE, ALEXANDER; TELLEZ-MARTINEZ, DAMIANA; DE ANDRADE, CLEVERTON ROBERTO; POLESI, MARISA CAMPOS; PORTUONDO, DEIVYS LEANDRO; CARLOS, IRACILDA ZEPPONE. Transient Foxp3(+) regulatory T-cell depletion enhances protective Th1/Th17 immune response in murine sporotrichosis caused by Sporothrix schenckii. Immunobiology, v. 225, n. 5, SEP 2020. (16/04250-0)