Parasite epigenetic memory and blood barriers dictate host transcriptional responses during generalist host-shifts

Parasitic infections are highly successful due to their ability to adapt to various host environments rapidly. Although avian models are commonly used to study host-parasite interactions, the effects of the foreign blood environment during cross-species infections are often overlooked. In this study, researchers investigated the impact of a heterologous blood matrix on the gene expression patterns of domestic canaries infected with the avian malaria parasite Plasmodium homocircumflexum (lineage COLL4).

To separate the influence of the blood matrix from the parasite itself, the researchers used a factorial experimental design. The findings revealed that mismatched transfusions resulted in significant and non-specific activation of the innate immune system, irrespective of the parasite's presence. After accounting for this background effect, the study observed distinct transcriptional patterns in the canaries.

The canaries that were previously infected with the same parasite (homologous infection) exhibited metabolic catalytic overload driven by key kinase hubs, such as AKT1 and CDK6. In contrast, canaries infected with a different parasite strain (heterologous infection) showed a shift towards structural and ribosomal regulation. These differences in host transcription, combined with the parasite's strain-specific transcription, indicate that early infection phases are heavily influenced by recent host-switching events.

The researchers conclude that this epigenetic memory plays a crucial role in determining virulence and proposes a new systems-based approach to understanding how pathogen history and compatibility between host and donor affect infection dynamics and molecular outcomes during colonization of novel ecological territories.