The Thymus in Chagas Disease: Molecular Interactions Involved in Abnormal T-Cell Migration and Differentiation

被引:7
作者
Perez, Ana Rosa [1 ,2 ]
de Meis, Juliana [3 ,4 ,5 ]
Rodriguez-Galan, Maria Cecilia [6 ]
Savino, Wilson [3 ,4 ,5 ]
机构
[1] Univ Nacl Rosario, CONICET, Inst Inmunol Clin & Expt Rosario, Rosario, Argentina
[2] Univ Nacl Rosario, Fac Ciencias Med, Ctr Invest & Prod React Biol, Rosario, Argentina
[3] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Thymus Res, Rio De Janeiro, Brazil
[4] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Natl Inst Sci & Technol Neuroimmunomodulat, Rio De Janeiro, Brazil
[5] Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Rio de Janeiro Res Network Neuroinflammat, Rio De Janeiro, Brazil
[6] Univ Nacl Cordoba, Fac Ciencias Quim, CONICET, Inmunol,CIBICI, Cordoba, Argentina
来源
FRONTIERS IN IMMUNOLOGY | 2020年 / 11卷
关键词
Chagas disease; thymocyte depletion; thymic epithelial cells; gene expression; cell adhesion and migration; TRYPANOSOMA-CRUZI INFECTION; POLYCLONAL LYMPHOCYTE-RESPONSES; V-BETA REPERTOIRE; TRANS-SIALIDASE; GLUCOCORTICOID-RECEPTOR; EXTRACELLULAR-MATRIX; THYMOCYTE DEPLETION; POSITIVE THYMOCYTES; INDUCED APOPTOSIS; EPITHELIAL-CELLS;
D O I
10.3389/fimmu.2020.01838
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Chagas disease, caused by the protozoan parasiteT. cruzi, is a prevalent parasitic disease in Latin America. Presently, it is spreading around the world by human migration, thus representing a new global health issue. Chronically infected individuals reveal a dissimilar disease progression: while nearly 60% remain without apparent disease for life, 30% develop life-threatening pathologies, such as chronic chagasic cardiomyopathy (CCC) or megaviscerae. Inflammation driven by parasite persistence seems to be involved in the pathophysiology of the disease. However, there is also evidence of the occurrence of autoimmune events, mainly caused by molecular mimicry and bystander activation. In experimental models of disease, is well-established thatT. cruziinfects the thymus and causes locally profound structural and functional alterations. The hallmark is a massive loss of CD4(+)CD8(+)double positive (DP) thymocytes, mainly triggered by increased levels of glucocorticoids, although other mechanisms seem to act simultaneously. Thymic epithelial cells (TEC) exhibited an increase in extracellular matrix deposition, which are related to thymocyte migratory alterations. Moreover, medullary TEC showed a decreased expression of AIRE and altered expression of microRNAs, which might be linked to a disrupted negative selection of the T-cell repertoire. Also, almost all stages of thymocyte development are altered, including an abnormal output of CD4(-)CD8(-)double negative (DN) and DP immature and mature cells, many of them carrying prohibited TCR-V beta segments. Evidence has shown that DN and DP cells with an activated phenotype can be tracked in the blood of humans with chronic Chagas disease and also in the secondary lymphoid organs and heart of infected mice, raising new questions about the relevance of these populations in the pathogenesis of Chagas disease and their possible link with thymic alterations and an immunoendocrine imbalance. Here, we discuss diverse molecular mechanisms underlying thymic abnormalities occurring duringT. cruziinfection and their link with CCC, which may contribute to the design of innovative strategies to control Chagas disease pathology.
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页数:20
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