Gene expression network analyses during infection with virulent and avirulent Trypanosoma cruzi strains unveil a role for fibroblasts in neutrophil recruitment and activation

dc.creatorOliveira, Antonio Edson R.
dc.creatorPereira, Milton C. A.
dc.creatorBelew, Ashton T.
dc.creatorFerreira, Ludmila R. P.
dc.creatorPereira, Larissa Marina Nogueira
dc.creatorNeves, Eula G. A.
dc.creatorNunes, Maria do Carmo P.
dc.creatorBurleigh, Barbara A.
dc.creatorDutra, Walderez Ornelas
dc.creatorEl-Sayed, Najib M.
dc.creatorGazzinelli, Ricardo Tostes
dc.creatorTeixeira, Santuza M. R.
dc.date2020-09-29T18:46:31Z
dc.date2020-09-29T18:46:31Z
dc.date2020
dc.date.accessioned2023-09-26T22:25:42Z
dc.date.available2023-09-26T22:25:42Z
dc.identifierOLIVEIRA, Antonio Edson R et al. Gene expression network analyses during infection with virulent and avirulentTrypanosoma cruzi strains unveil a role for fibroblasts in neutrophil recruitment and activation. PLoSPathog, v. 16, n. 8, e1008781, 2020. .https://doi.org/10.1371/journal.ppat.1008781
dc.identifier1553-7374
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/43693
dc.identifier10.1371/journal.ppat.1008781
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8879075
dc.descriptionChagas 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectParasitic diseases
dc.subjectTrypanosoma cruzi
dc.subjectNeutrophils
dc.subjectFibroblasts
dc.subjectCytokines
dc.subjectImmune response
dc.subjectGene expression
dc.subjectTranscriptome analysis
dc.titleGene expression network analyses during infection with virulent and avirulent Trypanosoma cruzi strains unveil a role for fibroblasts in neutrophil recruitment and activation
dc.typeArticle


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