W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
PLoS Pathog. 2011 Dec;7(12):e1002458. doi: 10.1371/journal.ppat.1002458. Epub 2011 Dec 22.
A causative agent of human malaria, Plasmodium falciparum, is transmitted by Anopheles mosquitoes. The malaria parasite is under intensive attack from the mosquito's innate immune system during its sporogonic development. We have used genetic engineering to create immune-enhanced Anopheles stephensi mosquitoes through blood meal-inducible expression of a transgene encoding the IMD pathway-controlled NF-kB Rel2 transcription factor in the midgut and fat-body tissue. Transgenic mosquitoes showed greater resistance to Plasmodium and microbial infection as a result of timely concerted tissue-specific immune attacks involving multiple effectors. The relatively weak impact of this genetic modification on mosquito fitness under laboratory conditions encourages further investigation of this approach for malaria control.
人类疟疾的病原体疟原虫由疟蚊传播。疟原虫在其孢子生殖发育过程中受到蚊子固有免疫系统的强烈攻击。我们利用基因工程技术,通过在中肠和脂肪体组织中诱导表达编码 IMD 途径控制的 NF-κB Rel2 转录因子的转基因,创建了免疫增强的斯氏按蚊。转基因蚊子由于涉及多种效应物的及时协调的组织特异性免疫攻击,对疟原虫和微生物感染表现出更强的抗性。这种遗传修饰对实验室条件下蚊子适应性的影响相对较弱,这鼓励进一步研究这种控制疟疾的方法。