Paracoccidioides brasiliensis infection promotes thymic disarrangement and premature egress of mature lymphocytes expressing prohibitive TCRs. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Di Gangi, Rosaria; Alves da Costa, Thiago; Thomé, Rodolfo; Peron, Gabriela; Burger, Eva; Verinaud, Liana
• Is Part Of: BMC infectious diseases. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 9
• Publication Date: 2016-12
• Subjects: Paracoccidioides brasiliensis -- Paracoccidioidomycosis -- Thymic atrophy; Communicable diseases -- Periodicals; Sexually Transmitted Diseases -- Periodicals; 616.905
• DOI: 10.1186/s12879-016-1561-8
• Languages: English
• ISSNs: 1471-2334

Abstract

Abstract Background Paracoccidioidomycosis, a chronic granulomatous fungal disease caused byParacoccidioides brasiliensis yeast cells affects mainly rural workers, albeit recently cases in immunosuppressed individuals has been reported. Protective immune response againstP. brasiliensis is dependent on the activity of helper T cells especially IFN-γ-producing Th1 cells. It has been proposed thatParacoccidioides 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 withP. 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 withParacoccidioides brasiliensis yeast cells promotes thymic alterations leading to a defective repertoire of peripheral T cells. The data presented here may represent new mechanisms by whichP. brasiliensis subverts the immune response towards the chronic infection observed in humans.