Insight into mRNA and its regulating pathways in the susceptibility and resistance to malaria infection by RNA sequencing

Abstract

Abstract Background: Malaria is a severe febrile sickness transmitted by Plasmodium parasites. During murine malaria infection, the host immune response exhibits distinct variations in response to two strains of Plasmodium yoelii (P. yoelii 17XL and P. yoelii XNL), which are known to be associated with varying levels of parasite virulence and malaria severity. The study focuses on change in molecular mechanisms that regulate transcriptional activity as well as the gene networks involved in pathogenesis and defence during lethal and non-lethal malaria infections at different time points. Methods: The gene expression profiles of mRNAs in control mice, Py.17XNL, and Py.17XL infected animals were evaluated using RNA sequencing and bioinformatics methods, and the differentially expressed mRNAs were validated using RT-qPCR. These DE mRNAs were identified as, cellular components, molecular functions, and biological processes utilizing Kyoto Encyclopaedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. Results: The results reveal several differentially expressed mRNAs that were associated with T-cell differentiation, cytokine receptor activity, and other related processes. Some of these genes, including Erfe, Hk1, and Podxl, are found to be significantly expressed in lethal infections, potentially contributing to increased parasitaemia and susceptibility. Conclusion: This study provides significant insights into the gene expression patterns that may be used to investigate the molecular mechanisms of the host's response to both lethal and non-lethal malaria infections. These mechanisms are involved in both the pathogenesis of the disease and the immune defence against malaria infection.