W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Dev Comp Immunol. 2013 Apr;39(4):323-32. doi: 10.1016/j.dci.2012.10.009. Epub 2012 Nov 22.
Malaria parasite transmission depends upon the successful development of Plasmodium in its Anopheles mosquito vector. The mosquito's innate immune system constitutes a major bottleneck for parasite population growth. We show here that in Anopheles gambiae, the midgut-specific transcription factor Caudal acts as a negative regulator in the Imd pathway-mediated immune response against the human malaria parasite Plasmodium falciparum. Caudal also modulates the mosquito midgut bacterial flora. RNAi-mediated silencing of Caudal enhanced the mosquito's resistance to bacterial infections and increased the transcriptional abundance of key immune effector genes. Interestingly, Caudal's silencing resulted in an increased lifespan of the mosquito, while it impaired reproductive fitness with respect to egg laying and hatching.
疟原虫的传播依赖于疟原虫在其按蚊媒介中的成功发育。蚊子的先天免疫系统是寄生虫种群增长的主要瓶颈。我们在这里表明,在冈比亚按蚊中,肠道特异性转录因子尾基因(Caudal)作为一种负调控因子,在 IMD 通路介导的针对人类疟原虫(Plasmodium falciparum)的免疫反应中起作用。Caudal 还调节了蚊子中肠的细菌菌群。Caudal 的 RNAi 介导沉默增强了蚊子对细菌感染的抵抗力,并增加了关键免疫效应基因的转录丰度。有趣的是,Caudal 的沉默导致蚊子寿命延长,而在产卵和孵化方面则损害了生殖适应性。