National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli, Taiwan.
Tropical Medicine Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Front Immunol. 2021 Mar 9;12:640367. doi: 10.3389/fimmu.2021.640367. eCollection 2021.
The C-type lectins, one family of lectins featuring carbohydrate binding domains which participate in a variety of bioprocesses in both humans and mosquitoes, including immune response, are known to target DENV. A human C-type lectin protein CLEC18A in particular shows extensive glycan binding abilities and correlates with type-I interferon expression, making CLEC18A a potential player in innate immune responses to DENV infection; this potential may provide additional regulatory point in improving mosquito immunity. Here, we established for the first time a transgenic line that expresses human CLEC18A. This expression enhanced the Toll immune pathway responses to DENV infection. Furthermore, viral genome and virus titers were reduced by 70% in the midgut of transgenic mosquitoes. We found significant changes in the composition of the midgut microbiome in CLEC18A expressing mosquitoes, which may result from the Toll pathway enhancement and contribute to DENV inhibition. Transgenic mosquito lines offer a compelling option for studying DENV pathogenesis, and our analyses indicate that modifying the mosquito immune system via expression of a human immune gene can significantly reduce DENV infection.
C 型凝集素是凝集素家族的一员，其具有参与人类和蚊子中多种生物过程的碳水化合物结合结构域，包括免疫反应，已知其可以靶向登革热病毒。特别是人类 C 型凝集素蛋白 CLEC18A 表现出广泛的聚糖结合能力，并与 I 型干扰素表达相关，这使其成为登革热病毒感染先天免疫反应的潜在参与者；这一潜力可能为提高蚊子免疫力提供了额外的调控点。在这里，我们首次建立了表达人 CLEC18A 的转基因系。这种表达增强了 Toll 免疫途径对登革热病毒感染的反应。此外，转基因蚊子的中肠中的病毒基因组和病毒滴度降低了 70%。我们发现表达 CLEC18A 的蚊子中肠微生物组的组成发生了显著变化，这可能是由于 Toll 途径的增强，并有助于抑制登革热病毒。转基因蚊子系为研究登革热病毒发病机制提供了一个引人注目的选择，我们的分析表明，通过表达人类免疫基因来修饰蚊子的免疫系统可以显著降低登革热病毒的感染。
