SRA

The transcriptional response of hosts to genetically similar pathogens can vary substantially, with important implications for disease severity and host fitness. A pathogen with low virulence can theoretically elicit both high and low host responses, as the outcome depends on both the effectiveness of the host at suppressing the pathogen and the ability of the pathogen to evade the immune system. Here, we investigate the transcriptional response of Eurasian siskins (Spinus spinus) to two closely related malaria parasite lineages. Birds were infected with either the high-virulent lineage Plasmodium relictum SGS1, the low-virulent sister lineage P. relictum GRW4, or sham-injected (controls). Blood samples for RNA-sequencing were collected at four time points during the course of infection, totalling 76 transcriptomes from 19 birds. Hosts infected with SGS1 experienced up to 87% parasitemia, major transcriptome shifts throughout the infection, and multiple genes showed strong correlation with parasitemia. In contrast, GRW4-infected hosts displayed low parasitemia (maximum 0.7%) with a minor transcriptional response. We further demonstrate that the baseline gene expression levels of hosts prior to infection were irrelevant as immunocompetence markers as they could not predict future pathogen load. This study shows that the magnitude of the host transcriptional response can differ markedly to related parasites with different virulence, and it enables a better understanding of the molecular interactions taking place between hosts and parasites.