Characterization of the innate and adaptive immune responses during the infection with Trichophyton rubrum

• Grant number: 10/19369-6
• Support type: Regular Research Grants
• Duration: April 01, 2011 - March 31, 2014
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Gil Benard
• Grantee: Gil Benard
• Home Institution: Instituto de Medicina Tropical de São Paulo (IMT). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Assoc. researchers: Carlos Pelleschi Taborda ; Maria da Gloria Sousa Stafocker ; Paulo Ricardo Criado ; Sandro Rogerio de Almeida

Abstract

Fungal infections have become an important public health problem in recent decades due to significant increases in the number of immunocompromised patients. These infections include superficial dermatophytosis which causes lesions of keratinized tissues such as skin, hair and nails in the immunocompetent host. In immunosuppressed patients more severe invasive infections have been described, which pose some challenge in their treatment. Little is known about the immunopathogenesis of this disease, although Trichophyton rubrum is its most common etiologic agent. Cells of the innate immune system detect pathogens through pattern recognition receptors (PRRs) such as the Toll-like receptors (TLRs) and C-type lectin receptors (CLRs). These receptors recognize pathogens and initiate protective immune responses during infection. Recently, a new subtype of T helper cells called Th17 cells was described. These cells are characterized by the secretion of IL-17, which is essential to mount an immune response against certain pathogens. It has been shown that some CLRs such as the mannose receptor and/or TLRs are able to regulate the balance between Th1 and Th17 immune responses in part by the release of cytokines secreted by Th17 cells. We propose to examine the involvement of TLR2, TLR4 and the mannose receptor in the recognition of T. rubrum, as well as the involvement of these receptors in the induction of Th1-Th17 responses in patients with dermatophytosis and healthy controls. In parallel, we propose to establish an experimental model of dermatophytosis in BALB/c mice to analyze the cell types involved in inflammatory responses in situ in these animals. This will facilitate the delineation of the mechanisms involved in the activation and suppression of the innate and adaptative immune responses mounted during dermatophytosis. (AU)

Scientific publications

(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)

DE SOUSA, MARIA DA GLORIA T.; SANTANA, GRAZIELLE B.; CRIADO, PAULO R.; BENARD, GIL. Chronic widespread dermatophytosis due to Trichophyton rubrum: a syndrome associated with a Trichophyton-specific functional defect of phagocytes. FRONTIERS IN MICROBIOLOGY, v. 6, AUG 6 2015. Web of Science Citations: 8.

DE OLIVEIRA, CRISTIANE BEATRIZ; VASCONCELLOS, CIDIA; SAKAI-VALENTE, NEUSA Y.; SOTTO, MIRIAN NACAGAMI; LUIZ, FERNANDA GUEDES; BELDA JUNIOR, WALTER; TEIXEIRA DE SOUSA, MARIA DA GLORIA; BENARD, GIL; CRIADO, PAULO RICARDO. TOLL-LIKE RECEPTORS (TLR) 2 AND 4 EXPRESSION OF KERATINOCYTES FROM PATIENTS WITH LOCALIZED AND DISSEMINATED DERMATOPHYTOSIS. Revista do Instituto de Medicina Tropical de São Paulo, v. 57, n. 1, p. 57-61, JAN-FEB 2015. Web of Science Citations: 9.