Changes in the thymic microenvironment by experimental Paracoccidioides brasiliensis infection

• Grant number: 13/08194-9
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2013
• End date: May 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Liana Maria Cardoso Verinaud
• Grantee: Liana Maria Cardoso Verinaud
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

The thymus is the lymphoid organ responsible for generating T lymphocytes and thus preserving its microenvironment is critical to the development and maintenance of robust immune responses. However, despite its importance, a number of factors, such as stress, poor nutrition, drugs used in treatment against cancers and infectious diseases, are able to promote changes in the thymic microenvironment leading to decreased ability of the individual to reconstruct their repertoire of peripheral T cells and respond to new antigens.Studies from our laboratory have shown that experimental infection with Paracoccidioides brasiliensis, the causative agent of the most prevalent systemic mycosis in South America and Central - with paracoccidioidomycosis (PCM), induces a picture of acute thymic atrophy, with invasion of the thymus by fungus . The main changes observed include: decreased body weight, degeneration of the cortical layer with an increased rate of apoptosis and autophagic cell death, loss of cortico-medullary demarcation and the presence of extensive inflammatory infiltrate in the sub-capsular layer. This deep thymic atrophy may be associated with functional alterations in cellular components, and soluble structural thymus, with high death of immature T cells (thymocytes or while the thymus), and also with early migration of immature cells to the periphery the immune system. Moreover, recently, the involvement of NLRP3 inflamassomas, macromolecular complexes involved in the inflammatory activation of caspases, has been suggested as essential both in thymic atrophy as the elimination of many pathogens.Thus, this project aims to analyze morphophysiological changes triggered in the thymus, as well as participation intrathymic inflammatory response during experimental infection with Paracoccidioides brasiliensis. (AU)

Scientific publications

(4)

(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)

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)

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)

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)