Differential Modulation of Mouse Heart Gene Expression by Infection With Two Trypanosoma cruzi Strains: a transcriptome analysis

Abstract

The causative agent of Chagas disease, Trypanosoma cruzi, retains high genetic diversity, and its populations vary greatly in different geographic locations. T. cruzi mammalian hosts, including humans, also have high genetic variation, making it difficult to predict the disease outcome. Accordingly, this variability must be taken into account in studies aiming to determine the effect of polyparasitism on drug trials, vaccine studies, diagnosis or basic research. Therefore, there is a growing need to consider the interaction between the pathogen and the host immune system in mixed infections. In the present work, we show an in-depth analysis of gene expression in hearts from BALB/c mice infected with either Col1.7G2 or JG alone or a mixture of both strains. Col1.7G2 induced a higher Th1 inflammatory response, while JG produced a weaker activation of immune response genes. Furthermore, JG-infected mice showed a notable reduction in the expression of genes responsible for mitochondrial oxidative phosphorylation and protein synthesis. Interestingly, the mixture-infected group displayed changes in gene expression caused by both strains. Overall, we provided new insights into the host-pathogen interaction in the context of single and dual infection by showing the remarkable differences in the modulation of host gene expression by the two T. cruzi strains.