Inflammation and cell death in thymic demise induced by Paracoccidioides brasiliensis

• Grant number: 12/22131-7
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: March 01, 2013
• End date: July 31, 2016
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Liana Maria Cardoso Verinaud
• Grantee: Thiago Alves da Costa
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The thymus is the primary lymphoid organ responsible for the development and maturation of T lymphocytes. To perform such role, the thymic microenvironment needs to be intact, and there should be a fine control of chemokines and growth factors released by epithelial cells, thymic dendritic cells and macrophages. However, the thymus can suffer involution under physiological conditions, e.g. in aging and pathologies, such as infections. Studies from our laboratory have shown that experimental infection with Paracoccidioides brasiliensis, the causative agent of the most prevalent systemic mycosis in South and Central America - the paracoccidioidomycosis, induces thymic atrophy, with loss of corticomedullary delimitation, depletion of cortical thymocytes, decreased ability in migration with retention of double-negative thymocytes, and the presence of inflammatory infiltrate composed of neutrophils and macrophages. The thymic atrophy observed may be related to (i) changes in the compartments of thymic stromal cells, (ii) increased death of thymocytes and (iii) premature migration of thymocytes to the periphery. Recently, the involvement of NLRP3 inflammasomes, macromolecular complexes involved in the inflammatory activation of caspases, has been suggested as essential in eliminating various pathogens and may be involved in thymic atrophy triggered by physiological aging. Thus, this project aims to analyze the early thymic atrophy observed during experimental infection with Paracoccidioides brasiliensis, the possible cell death pathways involved in the loss of thymocytes and the involvement of inflammatory pathways in this process, with emphasis on inflammasome NLRP3.

Scientific publications

(6)

(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)

DA COSTA, THIAGO ALVES; DI GANGI, ROSARIA; MARTINS, PAULA; FIGUEIREDO LONGHINI, ANA LEDA; ZANUCOLI, FABIO; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE; STACH-MACHADO, DAGMAR RUTH; BURGER, EVA; VERINAUD, LIANA; THOME, RODOLFO. Protection against Paracoccidioides brasiliensis infection in mice treated with modulated dendritic cells relies on inhibition of interleukin-10 production by CD8(+) T cells. Immunology, v. 146, n. 3, p. 486-495, NOV 2015. (13/08194-9, 12/22131-7, 13/01401-9, 11/17965-3, 14/02631-0)

DA COSTA, THIAGO ALVES; DI GANGI, ROSARIA; THOME, RODOLFO; FELISBINO, MARINA BARRETO; BONFANTI, AMANDA PIRES; WATANABE ISHIKAWA, LARISSA LUMI; SARTORI, ALEXANDRINA; BURGER, EVA; VERINAUD, LIANA. Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis. PLoS One, v. 11, n. 10, OCT 13 2016. (14/19492-3, 13/08194-9, 12/03238-5, 12/22131-7, 13/01401-9, 14/02631-0)

DI GANGI, ROSARIA; DA COSTA, THIAGO ALVES; THOME, RODOLFO; PERON, GABRIELA; BURGER, EVA; VERINAUD, LIANA. Paracoccidioides brasiliensis infection promotes thymic disarrangement and premature egress of mature lymphocytes expressing prohibitive TCRs. BMC INFECTIOUS DISEASES, v. 16, MAY 17 2016. (12/22131-7, 13/01401-9, 13/08194-9, 14/02631-0)

THOME, RODOLFO; ISSAYAMA, LUIDY K.; DA COSTA, THIAGO ALVES; GANGI, ROSARIA D.; FERREIRA, ISADORA T.; RAPOSO, CATARINA; LOPES, STEFANIE C. P.; DA CRUZ HOEFLING, MARIA ALICE; COSTA, FABIO T. M.; VERINAUD, LIANA. Dendritic cells treated with crude Plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation. Immunology, v. 143, n. 2, p. 164-173, OCT 2014. (12/22131-7, 13/01401-9, 11/13191-3, 11/17965-3)

THOME, RODOLFO; ISSAYAMA, LUIDY K.; DA COSTA, THIAGO ALVES; GANGI, ROSARIA D.; FERREIRA, ISADORA T.; RAPOSO, CATARINA; LOPES, STEFANIE C. P.; DA CRUZ HOEFLING, MARIA ALICE; COSTA, FABIO T. M.; VERINAUD, LIANA. Dendritic cells treated with crude Plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation. IMMUNOLOGY, v. 143, n. 2, p. 10-pg., 2014-10-01. (13/01401-9, 11/13191-3, 12/22131-7, 11/17965-3)

DA COSTA, THIAGO ALVES; DI GANGI, ROSARIA; MARTINS, PAULA; FIGUEIREDO LONGHINI, ANA LEDA; ZANUCOLI, FABIO; RODRIGUES DE OLIVEIRA, ALEXANDRE LEITE; STACH-MACHADO, DAGMAR RUTH; BURGER, EVA; VERINAUD, LIANA; THOME, RODOLFO. Protection against Paracoccidioides brasiliensis infection in mice treated with modulated dendritic cells relies on inhibition of interleukin-10 production by CD8(+) T cells. IMMUNOLOGY, v. 146, n. 3, p. 10-pg., 2015-11-01. (13/01401-9, 12/22131-7, 13/08194-9, 14/02631-0, 11/17965-3)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

COSTA, Thiago Alves da. Inflammation and cell death in thymic demise induced by Paracoccidioides brasiliensis. 2016. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.