Authors

Discussion

Toxoplasma gondii, a zoonotic apicomplexan that infects over a billion people worldwide, can cause early death in immunocompromised individuals and defects in foetal brain development. Toxoplasma is also a major cause of abortion in small ruminants. When Toxoplasma encounters host cells, several outcomes are possible, including parasite actively invading the cells, entering the cell via phagocytosis, or failing to enter the cell completely. These heterogenous outcomes occur simultaneously in the same host and likely play significant roles in disease pathogenesis. For example, only phagocytosed parasites are known to induce interleukin 12, which is central to host immune responses against the parasite. Yet, current knowledge of host-Toxoplasma interactions is largely based on averaged responses in bulk cell populations. Here, we employed single cell RNA (scRNA) and bulk RNA sequencing to investigate the transcriptional profiles that underpin heterogenous Toxoplasma interaction with human peripheral blood mononuclear cells (PBMCs). Our scRNA-seq showed Toxoplasma preferentially infects and elicits transcriptional responses in macrophages and dendritic cells in human blood. We also observed the differences in transcriptional responses between infected and bystander cells. Notably, we observed that cell-cell communication between monocytes, macrophages, and dendritic cells, drive transcriptional response to the parasite. Expectedly, using bulk RNA-sequencing data of heterogenous host-Toxoplasma interaction outcomes as reference panel, we observed that genes expressed in cells infected via phagocytosis are largely expressed in macrophages and dendritic cell single cell clusters. Overall, by integrating scRNA and bulk RNA sequencing, our study unveils the transcriptional profiles of immune cells in diverse infection outcomes, providing novel avenues for targeted investigations into gene functions and potential implications for therapeutic strategies.