Host-parasite interactions of an avian blood parasite elucidated by single-cell transcriptomics

To date, the intricate cellular and molecular interplay between hosts and parasites is well described for a limited number of model systems. Recent methodological advances now allow deep insights in non-model symbioses, including those that ultimately appear barely antagonistic and may entail intense reciprocal manipulations. We applied single cell RNA-sequencing to blood samples of a wild, long-lived avian host, the Common Buzzard (Buteo buteo), infected with the malaria-like parasite Leucocytozoon toddi. We identified host cell types and their respective molecular toolkits involved in both, host immunity and parasite virulence. Comparing blood cell-type specific transcriptomic profiles between Buzzards with low and high parasitaemia, we gain insights into the parasitic immune evasion and potential modulation of the host immune response. The immune response of immune cells was overall low under high parasitaemia. While this supposed downregulation affects anti-parasitic genes, genes upregulated under high parasitaemia are implicated in promoting parasite growth. In parasite-infected cells, networks of differentially expressed genes reveal patterns of host ribosome biogenesis that are strongly modulated between cell types and parasite densities. Furthermore, our findings suggest that L. toddi preferentially infects thrombocytes. Our study shows how mechanisms of virulence and immunosuppression are modified in a specialised parasite exhibiting low virulence as the result of long-lasting coevolution. In future studies, the cell-type specific markers identified will allow us to expand our scope beyond single cells and towards a more complete understanding of how host-parasite interactions affect the evolutionary forces shaping host immunity.