The First Contact of Human Dendritic Cells With Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central Pathway
Chagas disease is a debilitating and neglected disease caused by the protozoan Trypanosoma cruzi. Soon after infection, interactions among T. cruzi and host innate immunity cells can drive/contribute to disease outcome. Dendritic cells (DCs), present in all tissues, are one of the first immune cells...
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doaj-3e0c66d40aaa4b5fbbcf0d20b615b3ab2021-04-09T04:27:45ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-04-011210.3389/fimmu.2021.638020638020The First Contact of Human Dendritic Cells With Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central PathwayNatalia Gil-Jaramillo0Amanda Pereira Rocha1Tainá Raiol2Flávia Nader Motta3Flávia Nader Motta4Cecília Favali5Marcelo M. Brigido6Izabela M. D. Bastos7Jaime M. Santana8Laboratório de Interação Patógeno-Hospedeiro, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, BrazilLaboratório de Interação Patógeno-Hospedeiro, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, BrazilFiocruz Brasília–Gerência Regional de Brasília (GEREB), Fundação Oswaldo Cruz (Fiocruz), Brasília, BrazilLaboratório de Interação Patógeno-Hospedeiro, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, BrazilFaculdade de Ceilândia, Universidade de Brasília, Brasília, BrazilLaboratório de Imunologia Celular, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, BrazilLaboratório de Imunologia Molecular, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, BrazilLaboratório de Interação Patógeno-Hospedeiro, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, BrazilLaboratório de Interação Patógeno-Hospedeiro, Instituto de Ciências Biológicas, Universidade de Brasília, Brasília, BrazilChagas disease is a debilitating and neglected disease caused by the protozoan Trypanosoma cruzi. Soon after infection, interactions among T. cruzi and host innate immunity cells can drive/contribute to disease outcome. Dendritic cells (DCs), present in all tissues, are one of the first immune cells to interact with Trypanosoma cruzi metacyclic trypomastigotes. Elucidating the immunological events triggered immediately after parasite-human DCs encounter may aid in understanding the role of DCs in the establishment of infection and in the course of the disease. Therefore, we performed a transcriptomic analysis of a 12 h interaction between T. cruzi and MoDCs (monocyte-derived DCs) from three human donors. Enrichment analyses of the 468 differentially expressed genes (DEGs) revealed viral infection response as the most regulated pathway. Additionally, exogenous antigen processing and presentation through MHC-I, chemokine signaling, lymphocyte co-stimulation, metallothioneins, and inflammasome activation were found up-regulated. Notable, we were able to identify the increased gene expression of alternative inflammasome sensors such as AIM2, IFI16, and RIG-I for the first time in a T. cruzi infection. Both transcript and protein expression levels suggest proinflammatory cytokine production during early T. cruzi-DCs contact. Our transcriptome data unveil antiviral pathways as an unexplored process during T. cruzi-DC initial interaction, disclosing a new panorama for the study of Chagas disease outcomes.https://www.frontiersin.org/articles/10.3389/fimmu.2021.638020/fullChagas diseaseinflammasomemetacyclic trypomastigotestranscriptomevirus infection |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Natalia Gil-Jaramillo Amanda Pereira Rocha Tainá Raiol Flávia Nader Motta Flávia Nader Motta Cecília Favali Marcelo M. Brigido Izabela M. D. Bastos Jaime M. Santana |
spellingShingle |
Natalia Gil-Jaramillo Amanda Pereira Rocha Tainá Raiol Flávia Nader Motta Flávia Nader Motta Cecília Favali Marcelo M. Brigido Izabela M. D. Bastos Jaime M. Santana The First Contact of Human Dendritic Cells With Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central Pathway Frontiers in Immunology Chagas disease inflammasome metacyclic trypomastigotes transcriptome virus infection |
author_facet |
Natalia Gil-Jaramillo Amanda Pereira Rocha Tainá Raiol Flávia Nader Motta Flávia Nader Motta Cecília Favali Marcelo M. Brigido Izabela M. D. Bastos Jaime M. Santana |
author_sort |
Natalia Gil-Jaramillo |
title |
The First Contact of Human Dendritic Cells With Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central Pathway |
title_short |
The First Contact of Human Dendritic Cells With Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central Pathway |
title_full |
The First Contact of Human Dendritic Cells With Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central Pathway |
title_fullStr |
The First Contact of Human Dendritic Cells With Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central Pathway |
title_full_unstemmed |
The First Contact of Human Dendritic Cells With Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central Pathway |
title_sort |
first contact of human dendritic cells with trypanosoma cruzi reveals response to virus as an unexplored central pathway |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2021-04-01 |
description |
Chagas disease is a debilitating and neglected disease caused by the protozoan Trypanosoma cruzi. Soon after infection, interactions among T. cruzi and host innate immunity cells can drive/contribute to disease outcome. Dendritic cells (DCs), present in all tissues, are one of the first immune cells to interact with Trypanosoma cruzi metacyclic trypomastigotes. Elucidating the immunological events triggered immediately after parasite-human DCs encounter may aid in understanding the role of DCs in the establishment of infection and in the course of the disease. Therefore, we performed a transcriptomic analysis of a 12 h interaction between T. cruzi and MoDCs (monocyte-derived DCs) from three human donors. Enrichment analyses of the 468 differentially expressed genes (DEGs) revealed viral infection response as the most regulated pathway. Additionally, exogenous antigen processing and presentation through MHC-I, chemokine signaling, lymphocyte co-stimulation, metallothioneins, and inflammasome activation were found up-regulated. Notable, we were able to identify the increased gene expression of alternative inflammasome sensors such as AIM2, IFI16, and RIG-I for the first time in a T. cruzi infection. Both transcript and protein expression levels suggest proinflammatory cytokine production during early T. cruzi-DCs contact. Our transcriptome data unveil antiviral pathways as an unexplored process during T. cruzi-DC initial interaction, disclosing a new panorama for the study of Chagas disease outcomes. |
topic |
Chagas disease inflammasome metacyclic trypomastigotes transcriptome virus infection |
url |
https://www.frontiersin.org/articles/10.3389/fimmu.2021.638020/full |
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