Elin Videvall, Vaidas Palinauskas, Gediminas Valkiūnas, and Olof Hellgren (June 2020)
Host transcriptional responses show major differences to high- and low-virulent avian malaria parasites
“Host transcriptional responses to high- and low-virulent avian malaria parasites”
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When hosts are infected with pathogens, does the severity of the outcome depend on the host, the pathogen, or both? For example, does a mild infection result from a strong and efficient host response that is able to suppress the pathogen? Or is the host response directly related to the ability of the pathogen to proliferate?
Scientists from Lund University, Sweden, and the Nature Research Center, Lithuania, aimed to evaluate these questions in a bird–malaria system. They sequenced the expression levels of all genes in Eurasian siskins and measured their response to two closely related lineages of the same malaria parasite species. The birds showed large transcriptional responses to the high-virulent lineage Plasmodium relictum SGS1, but low responses to the low-virulent lineage Plasmodium relictum GRW4. The milder infection of GRW4 could therefore not be explained by a forceful host response suppressing the parasite, and the intensity of malaria infection could also not be explained by higher gene expression levels prior to infection. These results shed light on the different transcriptional response strategies used by hosts during malaria infection and open the door for further exploratory questions into the mechanisms that prevent low-virulent pathogens from proliferating.
Abstract
The transcriptional response of hosts to genetically similar pathogens can vary substantially, with important implications for disease severity and host fitness. A low pathogen load 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 lineages of the malaria parasite Plasmodium relictum. Birds were infected with either the high-virulent lineage P. 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, totaling 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.