RT info:eu-repo/semantics/article
T1 Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects
A1 Carmelo, Emma
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 López, Manuel Carlos
A2 Obstetricia y GinecologíaPediatría, Medicina Preventiva y Salud Pública, Toxicología y Medicina Legal y Forense y Parasitología
A2 Investigación en Parasitología
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 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 systemrelated genes has been analyzed using high-throughput qPCR in T. cruzi antigenstimulated 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 suchasantigen-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
YR 2021
FD 2021
LK http://riull.ull.es/xmlui/handle/915/37288
UL http://riull.ull.es/xmlui/handle/915/37288
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 19-jun-2024