RT info:eu-repo/semantics/bookPart
T1 Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects
A1 Gómez, Inmaculada
A1 Thomas, M. Carmen
A1 Palacios, Génesis
A1 Egui, Adriana
A1 Carrilero, Bartolomé
A1 Simón, Marina
A1 Valladares Hernández, Basilio
A1 Segovia, Manuel
A1 Carmelo, Emma
A1 López, Manuel Carlos
K1 chronic Chagas disease
K1 Trypanosoma cruzi
K1 transcriptional profiling
K1 high-throughput RT-qPCR
K1 immunological pathway
K1 biomarkers
K1 indeterminate form
AB Infection by the Trypanosoma cruzi parasite causes Chagas disease and triggers multipleimmune mechanisms in the host to combat the pathogen. Chagas disease has a variableclinical presentation and progression, producing in the chronic phase a fragile balancebetween the host immune response and parasite replication that keeps patients in aclinically silent asymptomatic stage for years. Since the parasite is intracellular andreplicates within cells, the cell-mediated response of the host adaptive immunity plays acritical role. This function is mainly orchestrated by T lymphocytes, which recognizeparasite antigens and promote specific functions to control the infection. However, little isknown about the immunological markers associated with this asymptomatic stage of thedisease. In this large-scale analysis, the differential expression of 106 immune systemrelatedgenes has been analyzed using high-throughput qPCR in T. cruzi antigenstimulatedPBMC from chronic Chagas disease patients with indeterminate form (IND)and healthy donors (HD) from endemic and non-endemic areas of Chagas disease. Thisanalysis revealed that there were no differences in the expression level of most genesunder study between healthy donors from endemic and non-endemic areas determinedby PCA and differential gene expression analysis. Instead, PCA revealed the existence ofdifferent expression profiles between IND patients and HD (p < 0.0001), dependent on the32 genes included in PC1. Differential gene expression analysis also revealed 23upregulated genes (expression fold change > 2) and 11 downregulated genes(expression fold change < 0.5) in IND patients versus HD. Enrichment analysis showedthat several upregulated genes in IND patients participate in relevant immunologicalpathways 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 therelevant immunological pathways that seem to be activated could represent potentialbiomarkers of the asymptomatic form of Chagas disease, helpful to diagnosis andinfection control.
PB Frontiers Media SA
YR 2022
FD 2022
LK http://riull.ull.es/xmlui/handle/915/37435
UL http://riull.ull.es/xmlui/handle/915/37435
LA en
NO Sousa, G. R., Chevillard, C., Poveda, C., Teixeira-Carvalho, A., eds. (2022). Novel Insights Into the Immune Mechanisms Associated With the Pathogenesis of Chagas Disease. Lausanne: Frontiers Media SA. doi: 10.3389/978-2-88976-391-7
DS Repositorio institucional de la Universidad de La Laguna
RD 30-jun-2024