靶向microRNA、LncRNA调控鸡先天免疫MyD88-依赖通路的抗菌机制

TLR4-MyD88-依赖通路是家禽先天免疫抵抗革兰氏阴性菌感染的主要方式，机体抗感染能力的高低与该通路的精细调控密切相关。本组前期研究初步发现，在肠炎沙门氏菌（SE）人工感染雏鸡的易感组和抗病组脾脏组织中，该信号通路的关键基因、通路相关microRNA和LncRNA表达量存在显著差异，由此推测免疫相关的micRNA和LncRNA参与调控了MyD88-依赖通路并发挥抗菌感染作用。基于这一假设，在已完成的SE感染雏鸡转录组测序数据的基础上，以通路关键节点基因为靶标，首先确定靶向microRNA的功能及调控作用，然后通过microRNA与LncRNA互作，筛选出共同调控靶基因的LncRNA，并利用RIP和c-Klan等技术，对靶向LncRNA进行功能解析，结合成体水平功能验证，系统揭示microRNA和LncRNA在鸡MyD88-依赖通路中的调控机制，为先天免疫抗菌机理和抗病育种提供理论依据。

TLR4-MyD88-dependent pathway is one of the important ways of host innate immune response against gram negative bacteria infection in chicken. The preliminary work of our group identified several significantly differential expressed genes, microRNAs and LncRNAs (long noncoding RNA) in the spleen of SPF chickens with susceptibility and resistance of Salmonella enterica (SE),respectively. Therefore we put forward a hypothesis that microRNA and LncRNA might be key players in MyD88-dependent pathway.In this project, based on the mRNA, microRNA and LncRNA sequencing data, we will firstly determine the functional and regulatory networks among the microRNAs and key genes. Secondly, the interactions between microRNA and LncRNA will be detectd. Lastly, the function of LncRNA will be examined deeply using the RNA-RIP and c-Klan technologies. And we will also identify the function of targeted microRNA and LncRNA in chicken embryos. In summary, this study will provide new theoretical support for understanding of mechanism of innate immune resistance to bacterial infection and basis to produce disease resistance poultry by planned breeding.