Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis

Author(s)

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

• Document type: Journal article
• Source: PLoS One; v. 11, n. 10 OCT 13 2016.
• Web of Science Citations: 1

Abstract

T cell maturation takes place within the thymus, a primary lymphoid organ that is commonly targeted during infections. Previous studies showed that acute infection with Paracoccidioides brasiliensis (Pb), the causative agent of paracoccidioidomycosis (PCM), promotes thymic atrophy that is associated with the presence of yeast cells in the organ. However, as human PCM is a chronic infection, it is imperative to investigate the consequences of Pb infection over the thymic structure and function in chronic infection. In this sense, we developed a new experimental model where Pb yeast cells are injected through the intraperitoneal route and mice are evaluated over 120 days of infection. Thymuses were analyzed in chronically infected mice and we found that the thymus underwent extensive morphological alterations and severe infiltration of P. brasiliensis yeast cells. Further analyses showed an altered phenotype and function of thymocytes that are commonly found in peripheral mature T lymphocytes. We also observed activation of the NLRP3 inflammasome in the thymus. Our data provide new information on the severe changes observed in the thymic microenvironment in a model of PCM that more closely mimics the human infection. (AU)

• FAPESP's process: 14/19492-3 - Influence of the mTOR, STAT1/3 and iNOS signaling pathways in the activity of tolerogenic dendritic cells
• Grantee: Liana Maria Cardoso Verinaud
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/08194-9 - Changes in the thymic microenvironment by experimental Paracoccidioides brasiliensis infection
• Grantee: Liana Maria Cardoso Verinaud
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/03238-5 - Effects of valproic acid and trichostatin A on chromatin organization and its regulation by epigenetic factors in HepG2 cells grown under hyperglycemic conditions
• Grantee: Marina Barreto Felisbino
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/22131-7 - Inflammation and cell death in thymic demise induced by Paracoccidioides brasiliensis
• Grantee: Thiago Alves da Costa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/01401-9 - Changes in the thymic microenvironment during the acute phase of experimental infection with Paracoccidioides brasiliensis
• Grantee: Rosária Di Gangi
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/02631-0 - Role of nitric oxide (NO) in the modulation of experimental autoimmune encephalomyelitis (EAE) after the adoptive transfer of tolerogenic dendritic cells: influence of the MyD88-mTOR-iNOS and STAT1/3-iNOS axis
• Grantee: Rodolfo Thomé
• Support Opportunities: Scholarships in Brazil - Post-Doctoral