Authors

Discussion

Infection with intracellular pathogens, such as Toxoplasma gondii, is a single cell problem where pathogen encounters with a population of same cell type can simultaneously produce responses that are both beneficial or detrimental in a host. Heterogenous host-pathogen encounters can also result in pathogen subsets with different phenotypic properties in the same host. Therefore, only when we transcend the population level averages of cellular responses to pathogens will we make significant progress in infectious disease biology. Toxoplasma interaction with immune cells can simultaneously produce distinct infection outcomes in the same host (actively invaded, phagocytosed, uninfected-injected and uninfected bystander cell). Current knowledge on Toxoplasma-host cell interaction is mostly based on averaged host cell and/or parasite responses from a bulk cell population. Here, we used single cell RNA sequencing (scRNA-seq) and bulk RNA sequencing to investigate the transcriptional profiles that underpin heterogenous Toxoplasma interaction with human peripheral blood mononuclear cells (PBMCs). From the scRNA-seq, we observed that macrophages and dendritic cells are not only preferentially infected by Toxoplasma, but also are the main cells that transcriptionally respond to the parasite in human blood. From the bulk RNA-sequencing, we observed heterogeneity in the transcriptional profiles of actively invaded and phagocytosed cells. We also report genes that are differentially expressed in these infection outcomes in human monocytic cells. Using differentially expressed genes from the bulk RNA-seq data as reference panel for the scRNA-seq data, we observed that macrophages and dendritic cells mainly express genes that are differentially expressed in cells infected via phagocytosis. This study provides important insight into the transcriptional profiles of immune cells at a single cell level and their different infection outcomes as well as opening new avenues to investigate the role of genes in disparate infection outcomes.