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GENE EXPRESSION NETWORK ANALYSES DURING INFECTION WITH VIRULENT AND AVIRULENT TRYPANOSOMA CRUZI STRAINS UNVEIL A ROLE FOR FIBROBLASTS IN NEUTROPHIL RECRUITMENT AND ACTIVATION
Trypanosoma cruzi
Neutrophils
Fibroblasts
Cytokines
Immune response
Gene expression
Transcriptome analysis
Autor
Afiliación
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil
Department of Cell Biology and Molecular Genetics and Center for Bioinformatics and Computational Biology. University of Maryland.College Park, Maryland, United States of America
Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Clínica Médica. Belo Horizonte, MG, Brazil
Department of Immunology and Infectious Diseases. Harvard T. H. Chan School of Public Health. Boston, MA, United States of America
Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil
Department of Cell Biology and Molecular Genetics and Center for Bioinformatics and Computational Biology., University of Maryland.College Park, Maryland, United States of America
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil
Department of Cell Biology and Molecular Genetics and Center for Bioinformatics and Computational Biology. University of Maryland.College Park, Maryland, United States of America
Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil
Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Faculdade de Medicina. Departamento de Clínica Médica. Belo Horizonte, MG, Brazil
Department of Immunology and Infectious Diseases. Harvard T. H. Chan School of Public Health. Boston, MA, United States of America
Universidade Federal de Minas Gerais. Departamento de Morfologia. Belo Horizonte, MG, Brazil
Department of Cell Biology and Molecular Genetics and Center for Bioinformatics and Computational Biology., University of Maryland.College Park, Maryland, United States of America
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil/Fundação Oswaldo Cruz. Instituto Rene Rachou. Belo Horizonte, MG, Brazil
Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brazil
Resumen en ingles
Chagas disease is caused by Trypanosoma cruzi, a protozoan parasite that has a heterogeneous population composed of a pool of strains with distinct characteristics, including variable levels of virulence. In previous work, transcriptome analyses of parasite genes after infection of human foreskin fibroblasts (HFF) with virulent (CL Brener) and non-virulent (CL-14) clones derived from the CL strain, revealed a reduced expression of genes encoding parasite surface proteins in CL-14 compared to CL Brener during the final steps of the intracellular differentiation from amastigotes to trypomastigotes. Here we analyzed changes in the expression of host genes during in vitro infection of HFF cells with the CL Brener and CL-14 strains by analyzing total RNA extracted from cells at 60 and 96 hours post-infection (hpi) with each strain, as well as from uninfected cells. Similar transcriptome profiles were observed at 60 hpi with both strains compared to uninfected samples. However, at 96 hpi, significant differences in the number and expression levels of several genes, particularly those involved with immune response and cytoskeleton organization, were observed. Further analyses confirmed the difference in the chemokine/cytokine signaling involved with the recruitment and activation of immune cells such as neutrophils upon T. cruzi infection. These findings suggest that infection with the virulent CL Brener strain induces a more robust inflammatory response when compared with the non-virulent CL-14 strain. Importantly, the RNA-Seq data also exposed an unexplored role of fibroblasts as sentinel cells that may act by recruiting neutrophils to the initial site of infection. This role for fibroblasts in the regulation of the inflammatory response during infection by T. cruzi was corroborated by measurements of levels of different chemokines/cytokines during in vitro infection and in plasma from Chagas disease patients as well as by neutrophil activation and migration assays.
Palabras clave en ingles
Parasitic diseasesTrypanosoma cruzi
Neutrophils
Fibroblasts
Cytokines
Immune response
Gene expression
Transcriptome analysis
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