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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Di Gangi, Rosaria [1] ; da Costa, Thiago Alves [1] ; Thome, Rodolfo [1] ; Peron, Gabriela [1] ; Burger, Eva [2] ; Verinaud, Liana [1]
Total Authors: 6
Affiliation:
[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
Total Affiliations: 2
Document type: Journal article
Source: BMC INFECTIOUS DISEASES; v. 16, MAY 17 2016.
Web of Science Citations: 2
Abstract

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)

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: 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: 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