Zhang Jian, Zhang Shuguang, Wang Yanyan, Xu Wenyue, Zhang Jingru, Jiang Haobo, Huang Fusheng
Department of Pathobiology, The Third Military Medical University, Chongqing, P. R. China.
Department of Entomology and Plant Pathology, Oklahoma State University, Stillwater, Oklahoma, United States of America.
PLoS One. 2014 Feb 24;9(2):e89473. doi: 10.1371/journal.pone.0089473. eCollection 2014.
Antimalarial 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 FINDINGS: We 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/SIGNIFICANCE: Our 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.
抗疟药物可能会影响蚊子对疟原虫的防御能力。我们之前的研究表明，硝喹可显著降低约氏疟原虫对斯氏按蚊的感染，但潜在机制尚不清楚。为了了解硝喹如何影响斯氏按蚊的传播能力，我们探究了不同处理后成年雌蚊的转录组，检查了基因表达谱的变化，并鉴定了受药物和寄生虫影响的转录本。
方法/主要发现：我们将大规模平行测序和数据分析（包括基因发现、表达谱分析和功能预测）扩展到感染疟原虫前后以及有无硝喹处理的斯氏按蚊。使用组装到特定重叠群中的读数数量来计算相对丰度（RAs），我们根据感染诱导、感染抑制、药物诱导和药物抑制的RA值差异，将组装的重叠群分为四组。我们发现血餐中的硝喹和疟原虫感染均改变了蚊子基因的转录，这些基因涉及多种过程，包括病原体识别、信号转导、酚氧化酶原激活作用、细胞骨架组装、细胞黏附和氧化应激。差异基因表达可能促进了斯氏按蚊对寄生虫的某些防御反应并降低了其感染性。
结论/意义：我们的研究表明，硝喹可能在基因转录水平上调节蚊子针对疟原虫感染的几种免疫机制。这凸显了更好地了解抗疟药物对寄生虫生存和传播影响的必要性。此外，我们的数据极大地丰富了重要流行病学媒介物种斯氏按蚊的现有序列信息。
