Differential Expression of microRNAs in Thymic Epithelial Cells from Trypanosoma cruzi Acutely Infected Mice: Putative Role in Thymic Atrophy.
A common feature seen in acute infections is a severe atrophy of the thymus. This occurs in the murine model of acute Chagas disease. Moreover, in thymuses from Trypanosoma cruzi acutely infected mice, thymocytes exhibit an increase in the density of fibronectin and laminin integrin-type receptors, with an increase in migratory response ex vivo. Thymic epithelial cells (TEC) play a major role in the intrathymic T cell differentiation. To date, the consequences of molecular changes promoted by parasite infection upon thymus have not been elucidated. Considering the importance of microRNA for gene expression regulation, 85 microRNAs (mRNAs) were analyzed in TEC from T. cruzi acutely infected mice. The infection significantly modulated 29 miRNAs and modulation of 9 was also dependent whether TEC sorted out from the thymus exhibited cortical or medullary phenotype. In silico analysis revealed that these miRNAs may control target mRNAs known to be responsible for chemotaxis, cell adhesion, and cell death. Considering that we sorted TEC in the initial phase of thymocyte loss, it is conceivable that changes in TEC miRNA expression profile are functionally related to thymic atrophy, providing new clues to better understanding the mechanisms of the thymic involution seen in experimental Chagas disease.
Laboratory on Thymus Research, Institute Oswaldo Cruz, Oswaldo Cruz Foundation , Rio de Janeiro , Brazil.
Leandra
L
Linhares-Lacerda
Laboratory on Thymus Research, Institute Oswaldo Cruz, Oswaldo Cruz Foundation , Rio de Janeiro , Brazil.
Cintia Cristina
CC
Palu
HIV/AIDS Clinical Research Center, National Institute of Infectious Diseases, Oswaldo Cruz Foundation , Rio de Janeiro , Brazil.
Marcelo
M
Ribeiro-Alves
The National Institute of Science and Technology for Structural Biology and Bioimaging, Federal University of Rio de Janeiro , Rio de Janeiro , Brazil.
Bruno Diaz
BD
Paredes
Department of Immunology, Microbiology Institute, Federal University of Rio de Janeiro , Rio de Janeiro , Brazil.
Alexandre
A
Morrot
Functional Genomics Unit, Institut Pasteur de Montevideo , Montevideo , Uruguay.
Maria Rosa
MR
Garcia-Silva
Functional Genomics Unit, Institut Pasteur de Montevideo , Montevideo , Uruguay.
Alfonso
A
Cayota
Laboratory on Thymus Research, Institute Oswaldo Cruz, Oswaldo Cruz Foundation , Rio de Janeiro , Brazil.
Wilson
W
Savino
Chagas disease; microRNA; thymic epithelial cell; thymocyte migration; thymus atrophy