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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Paracoccidioides brasiliensis infection promotes thymic disarrangement and premature egress of mature lymphocytes expressing prohibitive TCRs

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Autor(es):
Di Gangi, Rosaria [1] ; da Costa, Thiago Alves [1] ; Thome, Rodolfo [1] ; Peron, Gabriela [1] ; Burger, Eva [2] ; Verinaud, Liana [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, Inst Biol, Dept Struct & Funct Biol, Rua Monteiro Lobato, 255, Cidade Univ, Campinas, SP - Brazil
[2] Univ Fed Alfenas, Inst Ciencias Biomed, Alfenas, MG - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: BMC INFECTIOUS DISEASES; v. 16, MAY 17 2016.
Citações Web of Science: 2
Resumo

Background: Paracoccidioidomycosis, a chronic granulomatous fungal disease caused by Paracoccidioides brasiliensis yeast cells affects mainly rural workers, albeit recently cases in immunosuppressed individuals has been reported. Protective immune response against P. brasiliensis is dependent on the activity of helper T cells especially IFN-gamma-producing Th1 cells. It has been proposed that Paracoccidioides brasiliensis is able to modulate the immune response towards a permissive state and that the thymus plays a major role in it. Methods: In this paper, we show that acute infection of BALB/c mice with P. brasiliensis virulent isolate (Pb18) might cause alterations in the thymic environment as well as the prohibitive TCR-expressing T cells in the spleens. Results: After seven days of infection, we found yeast cells on the thymic stroma, the thymic epithelial cells (TEC) were altered regarding their spatial-orientation and inflammatory mediators gene expression was increased. Likewise, thymocytes (differentiating T cells) presented higher migratory ability in ex vivo experiments. Notwithstanding, P. brasiliensis-infected mice showed an increased frequency of prohibitive TCR-expressing T cells in the spleens, suggesting that the selection processes that occur in the thymus may be compromised during the acute infection. Conclusion: In this paper, for the first time, we show that acute infection with Paracoccidioides brasiliensis yeast cells promotes thymic alterations leading to a defective repertoire of peripheral T cells. The data presented here may represent new mechanisms by which P. brasiliensis subverts the immune response towards the chronic infection observed in humans. (AU)

Processo FAPESP: 13/08194-9 - Alterações no microambiente tímico durante a infecção experimental pelo Paracoccidioides brasiliensis
Beneficiário:Liana Maria Cardoso Verinaud
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 14/02631-0 - Papel do óxido nítrico (NO) na modulação da encefalomielite autoimune experimental (EAE) após transferência adotiva de células dendríticas tolerogênicas: influência dos eixos MyD88-mTOR-iNOS e STAT1/3-iNOS
Beneficiário:Rodolfo Thomé
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 13/01401-9 - Alterações no microambiente tímico durante a fase aguda da infecção experimental com Paracoccidioides brasiliensis
Beneficiário:Rosária Di Gangi
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 12/22131-7 - Inflamação e morte celular na atrofia tímica induzida pelo Paracoccidioides brasiliensis
Beneficiário:Thiago Alves da Costa
Linha de fomento: Bolsas no Brasil - Doutorado