Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects
Infection by the Trypanosoma cruzi parasite causes Chagas disease and triggers multiple immune mechanisms in the host to combat the pathogen. Chagas disease has a variable clinical presentation and progression, producing in the chronic phase a fragile balance between the host immune response and par...
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Format: | Article |
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Frontiers Media S.A.
2021-09-01
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Series: | Frontiers in Cellular and Infection Microbiology |
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Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2021.722984/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Inmaculada Gómez M. Carmen Thomas Génesis Palacios Adriana Egui Bartolomé Carrilero Marina Simón Basilio Valladares Basilio Valladares Manuel Segovia Emma Carmelo Emma Carmelo Manuel Carlos López |
spellingShingle |
Inmaculada Gómez M. Carmen Thomas Génesis Palacios Adriana Egui Bartolomé Carrilero Marina Simón Basilio Valladares Basilio Valladares Manuel Segovia Emma Carmelo Emma Carmelo Manuel Carlos López Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects Frontiers in Cellular and Infection Microbiology chronic Chagas disease Trypanosoma cruzi transcriptional profiling high-throughput RT-qPCR immunological pathway biomarkers |
author_facet |
Inmaculada Gómez M. Carmen Thomas Génesis Palacios Adriana Egui Bartolomé Carrilero Marina Simón Basilio Valladares Basilio Valladares Manuel Segovia Emma Carmelo Emma Carmelo Manuel Carlos López |
author_sort |
Inmaculada Gómez |
title |
Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects |
title_short |
Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects |
title_full |
Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects |
title_fullStr |
Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects |
title_full_unstemmed |
Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects |
title_sort |
differential expression of immune response genes in asymptomatic chronic chagas disease patients versus healthy subjects |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Cellular and Infection Microbiology |
issn |
2235-2988 |
publishDate |
2021-09-01 |
description |
Infection by the Trypanosoma cruzi parasite causes Chagas disease and triggers multiple immune mechanisms in the host to combat the pathogen. Chagas disease has a variable clinical presentation and progression, producing in the chronic phase a fragile balance between the host immune response and parasite replication that keeps patients in a clinically silent asymptomatic stage for years. Since the parasite is intracellular and replicates within cells, the cell-mediated response of the host adaptive immunity plays a critical role. This function is mainly orchestrated by T lymphocytes, which recognize parasite antigens and promote specific functions to control the infection. However, little is known about the immunological markers associated with this asymptomatic stage of the disease. In this large-scale analysis, the differential expression of 106 immune system-related genes has been analyzed using high-throughput qPCR in T. cruzi antigen-stimulated PBMC from chronic Chagas disease patients with indeterminate form (IND) and healthy donors (HD) from endemic and non-endemic areas of Chagas disease. This analysis revealed that there were no differences in the expression level of most genes under study between healthy donors from endemic and non-endemic areas determined by PCA and differential gene expression analysis. Instead, PCA revealed the existence of different expression profiles between IND patients and HD (p < 0.0001), dependent on the 32 genes included in PC1. Differential gene expression analysis also revealed 23 upregulated genes (expression fold change > 2) and 11 downregulated genes (expression fold change < 0.5) in IND patients versus HD. Enrichment analysis showed that several upregulated genes in IND patients participate in relevant immunological pathways such as antigen-dependent B cell activation, stress induction of HSP regulation, NO2-dependent IL12 pathway in NK cells, and cytokine-inflammatory response. The antigen-specific differential gene expression profile detected in these patients and the relevant immunological pathways that seem to be activated could represent potential biomarkers of the asymptomatic form of Chagas disease, helpful to diagnosis and infection control. |
topic |
chronic Chagas disease Trypanosoma cruzi transcriptional profiling high-throughput RT-qPCR immunological pathway biomarkers |
url |
https://www.frontiersin.org/articles/10.3389/fcimb.2021.722984/full |
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doaj-b0989beb75f4499ea2a053caa9c8ca6a2021-09-06T04:19:31ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-09-011110.3389/fcimb.2021.722984722984Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy SubjectsInmaculada Gómez0M. Carmen Thomas1Génesis Palacios2Adriana Egui3Bartolomé Carrilero4Marina Simón5Basilio Valladares6Basilio Valladares7Manuel Segovia8Emma Carmelo9Emma Carmelo10Manuel Carlos López11Instituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Granada, SpainInstituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Granada, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, La Laguna, SpainInstituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Granada, SpainUnidad Regional de Medicina Tropical, Hospital Universitario Virgen de la Arrixaca, Murcia, SpainUnidad Regional de Medicina Tropical, Hospital Universitario Virgen de la Arrixaca, Murcia, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, La Laguna, SpainDepartamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, La Laguna, SpainUnidad Regional de Medicina Tropical, Hospital Universitario Virgen de la Arrixaca, Murcia, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, La Laguna, SpainDepartamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, La Laguna, SpainInstituto de Parasitología y Biomedicina López-Neyra, Consejo Superior de Investigaciones Científicas, Granada, SpainInfection by the Trypanosoma cruzi parasite causes Chagas disease and triggers multiple immune mechanisms in the host to combat the pathogen. Chagas disease has a variable clinical presentation and progression, producing in the chronic phase a fragile balance between the host immune response and parasite replication that keeps patients in a clinically silent asymptomatic stage for years. Since the parasite is intracellular and replicates within cells, the cell-mediated response of the host adaptive immunity plays a critical role. This function is mainly orchestrated by T lymphocytes, which recognize parasite antigens and promote specific functions to control the infection. However, little is known about the immunological markers associated with this asymptomatic stage of the disease. In this large-scale analysis, the differential expression of 106 immune system-related genes has been analyzed using high-throughput qPCR in T. cruzi antigen-stimulated PBMC from chronic Chagas disease patients with indeterminate form (IND) and healthy donors (HD) from endemic and non-endemic areas of Chagas disease. This analysis revealed that there were no differences in the expression level of most genes under study between healthy donors from endemic and non-endemic areas determined by PCA and differential gene expression analysis. Instead, PCA revealed the existence of different expression profiles between IND patients and HD (p < 0.0001), dependent on the 32 genes included in PC1. Differential gene expression analysis also revealed 23 upregulated genes (expression fold change > 2) and 11 downregulated genes (expression fold change < 0.5) in IND patients versus HD. Enrichment analysis showed that several upregulated genes in IND patients participate in relevant immunological pathways such as antigen-dependent B cell activation, stress induction of HSP regulation, NO2-dependent IL12 pathway in NK cells, and cytokine-inflammatory response. The antigen-specific differential gene expression profile detected in these patients and the relevant immunological pathways that seem to be activated could represent potential biomarkers of the asymptomatic form of Chagas disease, helpful to diagnosis and infection control.https://www.frontiersin.org/articles/10.3389/fcimb.2021.722984/fullchronic Chagas diseaseTrypanosoma cruzitranscriptional profilinghigh-throughput RT-qPCRimmunological pathwaybiomarkers |