Abstract
Malaria parasites are highly virulent pathogens which infect a wide range of vertebrates. Despite their importance, the way different hosts control and suppress malaria infections remains poorly understood. With recent developments in next-generation sequencing techniques, however, it is now possible to quantify the response of the entire transcriptome to infections. We experimentally infected Eurasian siskins (Carduelis spinus) with avian malaria parasites (Plasmodium ashfordi), and used high-throughput RNA-sequencing to measure the avian transcriptome in blood collected before infection (day 0), during peak parasitemia (day 21 postinfection), and when parasitemia was decreasing (day 31). We found considerable differences in the transcriptomes of infected and uninfected individuals, with a large number of genes differentially expressed during both peak and decreasing parasitemia stages. These genes were overrepresented among functions involved in the immune system, stress response, cell death regulation, metabolism, and telomerase activity. Comparative analyses of the differentially expressed genes in our study to those found in other hosts of malaria (human and mouse) revealed a set of genes that are potentially involved in highly conserved evolutionary responses to malaria infection. By using RNA-sequencing we gained a more complete view of the host response, and were able to pinpoint not only well-documented host genes but also unannotated genes with clear significance during infection, such as microRNAs. This study shows how the avian blood transcriptome shifts in response to malaria infection, and we believe that it will facilitate further research into the diversity of molecular mechanisms that hosts utilize to fight malaria infections.
Highlights
Malaria parasites (Plasmodium spp.) are intracellular apicomplexan protists that are most commonly known because they cause the disease malaria in an estimated 200 million people every year, resulting in over 600,000 deaths (WHO 2013)
We examined the response of the avian transcriptome to experimental malaria infections in vivo using RNA-seq
We examined whether there were overall transcriptome differences between infected and uninfected samples using a multidimensional scaling approach in the form of a principal component analysis (PCA)
Summary
Malaria parasites (Plasmodium spp.) are intracellular apicomplexan protists that are most commonly known because they cause the disease malaria in an estimated 200 million people every year, resulting in over 600,000 deaths (WHO 2013) These parasites are transmitted through dipteran vectors to an extremely diverse range of vertebrate hosts including primates, bats, rodents, reptiles, and birds (Garnham 1966; Levine 1988). Most of the research on molecular host responses to malaria have concentrated on humans and laboratory mice. Inbred laboratory mice strains are well suited for infection experiments, they have been artificially selected and cannot accurately represent natural host responses in other vertebrate taxa, including humans (White et al 2010). Considering that many major malaria discoveries have historically been made in species other than humans (Cox 2010), several of them in birds, studies encompassing a broader host diversity are likely to provide important advances in malaria research
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