Abstract
BackgroundAntimalarial drugs may impact mosquito’s defense against Plasmodium parasites. Our previous study showed nitroquine significantly reduced infection of Anopheles stephensi by Plasmodium yoelii, but the underlying mechanism remains unclear. In order to understand how transmission capacity of An. stephensi was affected by nitroquine, we explored the transcriptome of adult females after different treatments, examined changes in gene expression profiles, and identified transcripts affected by the drug and parasite.Methodology/Principal FindingsWe extended massively parallel sequencing and data analysis (including gene discovery, expression profiling, and function prediction) to An. stephensi before and after Plasmodium infection with or without nitroquine treatment. Using numbers of reads assembled into specific contigs to calculate relative abundances (RAs), we categorized the assembled contigs into four groups according to the differences in RA values infection induced, infection suppressed, drug induced, and drug suppressed. We found both nitroquine in the blood meal and Plasmodium infection altered transcription of mosquito genes implicated in diverse processes, including pathogen recognition, signal transduction, prophenoloxidase activation, cytoskeleton assembling, cell adhesion, and oxidative stress. The differential gene expression may have promoted certain defense responses of An. stephensi against the parasite and decreased its infectivity.Conclusions/SignificanceOur study indicated that nitroquine may regulate several immune mechanisms at the level of gene transcription in the mosquito against Plasmodium infection. This highlights the need for better understanding of antimalarial drug’s impact on parasite survival and transmission. In addition, our data largely enriched the existing sequence information of An. stephensi, an epidemiologically important vector species.
Highlights
Malaria parasites go through major transitions of differentiation as they cross tissue barriers of the mosquito with dramatic number changes [1,2]: between gametocytes and ookinetes, between ookinetes and mature oocysts, and between midgut and salivary gland sporozoites [3]
Using the model system of Plasmodium yoelii and Anopheles stephensi, we demonstrated that nitroquine induced transcription of a few mosquito genes encoding pattern recognition receptors, signal transducers, cell adhesion molecules, and oxidative stress proteins
Four-day-old adult females (25 per group) were allowed to blood fed on one of the following four groups: uninfected BALB/c mice treated with nitroquine (12 mg/kg) (UD, uninfected mice treated with nitroquine) for 4 h, P. yoelii-infected mice treated with the drug (12 mg/kg) (ID, infected mice treated with nitroquine) for 4 h, uninfected mice treated with buffer without nitroquine (UB, uninfected mice treated with buffer) for 4 h, or P. yoelii-infected mice treated with buffer only (IB, infected mice treated with buffer) for 4 h
Summary
Malaria parasites go through major transitions of differentiation as they cross tissue barriers of the mosquito with dramatic number changes [1,2]: between gametocytes and ookinetes, between ookinetes and mature oocysts, and between midgut and salivary gland sporozoites [3]. Digestive enzymes and mosquito defense proteins are partly responsible for the parasite loss at this stage [5,6]. The latter includes pathogen recognition proteins, serine proteases, phenoloxidases, antimicrobial peptides, and others. Effects of antimalarial drugs on infectivity of parasites in mosquitoes are well documented. Nitroquine is highly effective against P. yoelii, P. gallinaceum, and P. cynomolgi at the erythrocytic and exoerythrocytic stages. It interferes with structure and function of the cytoplasm and nucleus of P. yoelii exoerythrocytic forms [9]. Antimalarial drugs may impact mosquito’s defense against Plasmodium parasites. In order to understand how transmission capacity of An. stephensi was affected by nitroquine, we explored the transcriptome of adult females after different treatments, examined changes in gene expression profiles, and identified transcripts affected by the drug and parasite
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