Anopheles gambiae immune responses to human and rodent Plasmodium parasite species.
Anopheles gambiae immune responses to human and rodent Plasmodium parasite species.
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DOI：
10.1371/journal.ppat.0020052
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发表时间：
2006-06
期刊：
影响因子：
6.7
通讯作者：
Dimopoulos G
中科院分区：
文献类型：
--
作者：
Dong Y;Aguilar R;Xi Z;Warr E;Mongin E;Dimopoulos G
疟疾的传播取决于疟原虫在按蚊媒介中成功完成生命周期。主要的障碍是在中肠组织中遇到的，大多数寄生虫在那里被蚊子的免疫系统杀死。在本研究中，DNA微阵列分析已被用来比较冈比亚按蚊入侵的中肠上皮细胞的动合子阶段的人类病原体恶性疟原虫和啮齿动物实验模型病原体伯氏疟原虫的反应。伯氏疟原虫的入侵对蚊子的转录组产生了更深远的影响，包括各种功能基因类别，而恶性疟原虫在基因转录水平上引发了更广泛的免疫反应。摄入缺乏侵入性动合子的人类疟疾感染血液也诱导了多种免疫基因，包括几种抗疟原虫因子。使用RNAi基因沉默测定评估了12个选定的基因对寄生虫物种和细菌感染的影响，发现其中7个基因影响蚊子对两种寄生虫物种的抗性。MD2样受体AgMDL1和免疫凝集素FBN39仅在调节对恶性疟原虫的抗性方面表现出特异性，而抗微生物肽gambicin和一种新的推定短分泌肽IRSP5在防御啮齿动物寄生虫伯氏疟原虫方面更具特异性。虽然所有影响疟原虫发育的基因也会影响蚊子对细菌感染的抵抗力，但其中四种抗菌基因对疟原虫发育没有影响。本研究表明，恶性疟原虫和伯氏疟原虫感染对A.冈比亚疟原虫在基因转录水平上的生物学是相当多样的，并且对两种疟原虫的防御是由具有通用和疟原虫种特异性活性的抗微生物因子介导的。此外，我们的数据表明，蚊子能够在没有入侵动合子的情况下感知受感染的血液成分，从而诱导抗疟原虫免疫反应。疟疾寄生虫疟原虫必须穿过按蚊的肠壁才能完成其生命周期并在宿主之间传播。在感染的中肠阶段，蚊子激活免疫反应以消除大多数入侵的寄生虫。这些免疫应答的特征还不是很清楚，主要使用啮齿动物寄生虫模型伯氏疟原虫进行检查。在这里，作者研究了冈比亚按蚊对人类病原体恶性疟原虫、啮齿类寄生虫伯氏疟原虫的反应与细菌感染之间的关系，包括基因表达和功能水平。蚊子对这些病原体的反应是相当不同的，对两种疟原虫的防御涉及共同和物种特异性成分。即使在没有中肠入侵的情况下，疟疾感染的血液也足以激活抗疟原虫免疫反应。通过这种机制，蚊子可以在侵入肠道之前启动对疟原虫的防御。可能对疟原虫发育产生负面影响的蚊子基因也能够调节对细菌感染的抵抗力，但一些抗菌基因对疟原虫没有影响;因此，蚊子显然利用其抗菌防御系统对抗疟原虫。
Transmission of malaria is dependent on the successful completion of the Plasmodium lifecycle in the Anopheles vector. Major obstacles are encountered in the midgut tissue, where most parasites are killed by the mosquito's immune system. In the present study, DNA microarray analyses have been used to compare Anopheles gambiae responses to invasion of the midgut epithelium by the ookinete stage of the human pathogen Plasmodium falciparum and the rodent experimental model pathogen P. berghei. Invasion by P. berghei had a more profound impact on the mosquito transcriptome, including a variety of functional gene classes, while P. falciparum elicited a broader immune response at the gene transcript level. Ingestion of human malaria-infected blood lacking invasive ookinetes also induced a variety of immune genes, including several anti-Plasmodium factors. Twelve selected genes were assessed for effect on infection with both parasite species and bacteria using RNAi gene silencing assays, and seven of these genes were found to influence mosquito resistance to both parasite species. An MD2-like receptor, AgMDL1, and an immunolectin, FBN39, showed specificity in regulating only resistance to P. falciparum, while the antimicrobial peptide gambicin and a novel putative short secreted peptide, IRSP5, were more specific for defense against the rodent parasite P. berghei. While all the genes that affected Plasmodium development also influenced mosquito resistance to bacterial infection, four of the antimicrobial genes had no effect on Plasmodium development. Our study shows that the impact of P. falciparum and P. berghei infection on A. gambiae biology at the gene transcript level is quite diverse, and the defense against the two Plasmodium species is mediated by antimicrobial factors with both universal and Plasmodium-species specific activities. Furthermore, our data indicate that the mosquito is capable of sensing infected blood constituents in the absence of invading ookinetes, thereby inducing anti-Plasmodium immune responses. The malarial parasite Plasmodium has to traverse the gut wall of the Anopheles mosquito in order to complete its lifecycle and to be transmitted between hosts. At the midgut stage of infection, the mosquito activates immune responses to eliminate most invading parasites. The features of these immune responses are not very well understood and have mainly been examined using the rodent parasite model P. berghei. Here the authors investigated the relationship between the Anopheles gambiae responses against the human pathogen P. falciparum, the rodent parasite P. berghei, and bacterial infections, at both the gene expression and functional levels. The mosquito responses against these pathogens were quite diverse, and the defense against the two malaria parasite species involved both common and species-specific components. Malaria-infected blood was sufficient to activate anti-Plasmodium immune responses, even in the absence of midgut invasion. Through this mechanism, the mosquito can initiate its defense against Plasmodium prior to invasion of the gut. Mosquito genes that could negatively influence Plasmodium development were also capable of regulating the resistance to bacterial infection, but several of the antibacterial genes had no effect on Plasmodium; thus, the mosquito apparently utilizes its antibacterial defense systems against the malaria parasite.
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影响因子：
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