scholarly journals Differential Expression of Immune Response Genes in Asymptomatic Chronic Chagas Disease Patients Versus Healthy Subjects

Author(s):  
Inmaculada Gómez ◽  
M. Carmen Thomas ◽  
Génesis Palacios ◽  
Adriana Egui ◽  
Bartolomé Carrilero ◽  
...  

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.

Ecotoxicology ◽  
2011 ◽  
Vol 21 (1) ◽  
pp. 213-224 ◽  
Author(s):  
Sara C. Novais ◽  
Clara F. Howcroft ◽  
Laura Carreto ◽  
Patrícia M. Pereira ◽  
Manuel A. S. Santos ◽  
...  

Viruses ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 46 ◽  
Author(s):  
Yi-Sheng Sun ◽  
Zhang-Nv Yang ◽  
Fang Xu ◽  
Chen Chen ◽  
Hang-Jing Lu ◽  
...  

Enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) are the two most important pathogens of hand, foot, and mouth disease (HFMD). However, the neuropathogenesis of EV71 and CVA16 has not been elucidated. In our previous study, we established gerbils as a useful model for both EV71 and CVA16 infection. In this work, we used RNA-seq technology to analyze the global gene expression of the brainstem of EV71- and CVA16-infected gerbils. We found that 3434 genes were upregulated while 916 genes were downregulated in EV71-infected gerbils. In CVA16-infected gerbils, 1039 genes were upregulated, and 299 genes were downregulated. We also found significant dysregulation of cytokines, such as IP-10 and CXCL9, in the brainstem of gerbils. The expression levels of 10 of the most upregulated genes were confirmed by real-time RT-PCR, and the upregulated tendency of most genes was in accordance with the differential gene expression (DGE) results. Our work provided global gene expression analysis of virus-infected gerbils and laid a solid foundation for elucidating the neuropathogenesis mechanisms of EV71 and CVA16.


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