PMID- 33897690 OWN - NLM STAT- MEDLINE DCOM- 20210923 LR - 20240401 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - The First Contact of Human Dendritic Cells With Trypanosoma cruzi Reveals Response to Virus as an Unexplored Central Pathway. PG - 638020 LID - 10.3389/fimmu.2021.638020 [doi] LID - 638020 AB - 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. CI - Copyright (c) 2021 Gil-Jaramillo, Rocha, Raiol, Motta, Favali, Brigido, Bastos and Santana. FAU - Gil-Jaramillo, Natalia AU - Gil-Jaramillo N AD - Laboratorio de Interacao Patogeno-Hospedeiro, Instituto de Ciencias Biologicas, Universidade de Brasilia, Brasilia, Brazil. FAU - Rocha, Amanda Pereira AU - Rocha AP AD - Laboratorio de Interacao Patogeno-Hospedeiro, Instituto de Ciencias Biologicas, Universidade de Brasilia, Brasilia, Brazil. FAU - Raiol, Taina AU - Raiol T AD - Fiocruz Brasilia-Gerencia Regional de Brasilia (GEREB), Fundacao Oswaldo Cruz (Fiocruz), Brasilia, Brazil. FAU - Motta, Flavia Nader AU - Motta FN AD - Laboratorio de Interacao Patogeno-Hospedeiro, Instituto de Ciencias Biologicas, Universidade de Brasilia, Brasilia, Brazil. AD - Faculdade de Ceilandia, Universidade de Brasilia, Brasilia, Brazil. FAU - Favali, Cecilia AU - Favali C AD - Laboratorio de Imunologia Celular, Instituto de Ciencias Biologicas, Universidade de Brasilia, Brasilia, Brazil. FAU - Brigido, Marcelo M AU - Brigido MM AD - Laboratorio de Imunologia Molecular, Instituto de Ciencias Biologicas, Universidade de Brasilia, Brasilia, Brazil. FAU - Bastos, Izabela M D AU - Bastos IMD AD - Laboratorio de Interacao Patogeno-Hospedeiro, Instituto de Ciencias Biologicas, Universidade de Brasilia, Brasilia, Brazil. FAU - Santana, Jaime M AU - Santana JM AD - Laboratorio de Interacao Patogeno-Hospedeiro, Instituto de Ciencias Biologicas, Universidade de Brasilia, Brasilia, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210409 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (AIM2 protein, human) RN - 0 (Cytokines) RN - 0 (DNA-Binding Proteins) RN - 0 (Nuclear Proteins) RN - 0 (Phosphoproteins) RN - 0 (Receptors, Immunologic) RN - 148998-64-5 (IFI16 protein, human) RN - EC 3.6.1.- (RIGI protein, human) RN - EC 3.6.4.13 (DEAD Box Protein 58) SB - IM MH - Adult MH - Antigen Presentation/immunology MH - Chagas Disease/*immunology MH - Cytokines/metabolism MH - DEAD Box Protein 58/metabolism MH - DNA-Binding Proteins/metabolism MH - Dendritic Cells/*immunology MH - Female MH - Gene Expression Profiling MH - Gene Expression Regulation/genetics/immunology MH - Humans MH - Lymphocyte Activation/immunology MH - Male MH - Nuclear Proteins/metabolism MH - Phosphoproteins/metabolism MH - Receptors, Immunologic/metabolism MH - T-Lymphocytes/*immunology MH - Transcriptome/genetics MH - Trypanosoma cruzi/*immunology MH - Virus Diseases/*immunology MH - Young Adult PMC - PMC8062726 OTO - NOTNLM OT - Chagas disease OT - inflammasome OT - metacyclic trypomastigotes OT - transcriptome OT - virus infection COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/04/27 06:00 MHDA- 2021/09/24 06:00 PMCR- 2021/01/01 CRDT- 2021/04/26 05:49 PHST- 2020/12/04 00:00 [received] PHST- 2021/03/11 00:00 [accepted] PHST- 2021/04/26 05:49 [entrez] PHST- 2021/04/27 06:00 [pubmed] PHST- 2021/09/24 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.638020 [doi] PST - epublish SO - Front Immunol. 2021 Apr 9;12:638020. doi: 10.3389/fimmu.2021.638020. eCollection 2021.