title: Severe Changes in Thymic Microenvironment in a Chronic Experimental Model of Paracoccidioidomycosis.
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.
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Alves da Costa
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Rosária
authors.initials: R
authors.lastname: Di Gangi
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Thomé
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Marina
authors.initials: M
authors.lastname: Barreto Felisbino
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Amanda
authors.initials: A
authors.lastname: Pires Bonfanti
authors.affiliation: Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
authors.forename: Larissa
authors.initials: L
authors.lastname: Lumi Watanabe Ishikawa
authors.affiliation: Department of Microbiology and Immunology, Institute of Biosciences of Botucatu, Univ. Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
authors.forename: Alexandrina
authors.initials: A
authors.lastname: Sartori
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedical Sciences, Federal University of Alfenas (UNIFAL-MG), Alfenas, Minas Gerais, Brazil.
authors.forename: Eva
authors.initials: E
authors.lastname: Burger
authors.affiliation: Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors.forename: Liana
authors.initials: L
authors.lastname: Verinaud
mesh_terms: D000818:Animals; D017209:Apoptosis; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D058847:Inflammasomes / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010228:Paracoccidioides / Q000472:pathogenicity*; D010229:Paracoccidioidomycosis / Q000382:microbiology / Q000473:pathology*; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000378:metabolism* / Q000473:pathology
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D053181:Caspase 8