Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects
Date
2022Abstract
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 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.