Expression of Network Medicine-Predicted Genes in Human Macrophages Infected with Leishmania major

Abstract

Leishmania spp. commonly infects phagocytic cells of the immune system, particularly macrophages, employing various immune evasion strategies that enable their survival by altering the intracellular environment. In mammals, these parasites establish persistent infections by modulating gene expression in macrophages, thus interfering with immune signaling and response pathways, ultimately creating a favorable environment for the parasite’s survival and reproduction. In this study, our objective was to use data mining and subsequent filtering techniques to identify the genes that play a crucial role in the infection process of Leishmania spp. We aimed to pinpoint genes that have the potential to influence the progression of Leishmania infection. To achieve this, we exploited prior, curated knowledge from major databases and constructed 16 datasets of human molecular information consisting of coding genes and corresponding proteins. We obtained over 400 proteins, identifying approximately 200 genes. The proteins coded by these genes were subsequently used to build a network of protein–protein interactions, which enabled the identification of key players; we named this set Predicted Genes. Then, we selected approximately 10% of Predicted Genes for biological validation. THP-1 cells, a line of human macrophages, were infected with Leishmania major in vitro for the validation process. We observed that L. major has the capacity to impact crucial genes involved in the immune response, resulting in macrophage inactivation and creating a conducive environment for the survival of Leishmania parasites.