State Key laboratory for Conservation and Utilization of Bio-Resources in Yunnan, 12635 Yunnan University , Kunming, Yunnan, China.
Innate Immun. 2017 Nov;23(8):656-666. doi: 10.1177/1753425917732822. Epub 2017 Sep 29.
The genetically tractable organism Caenorhabditis elegans is a powerful model animal for the study of host innate immunity. Although the intestine and the epidermis of C. elegans that is in contact with pathogens are likely to function as sites for the immune function, recent studies indicate that the nervous system could control innate immunity in C. elegans. In this report, we demonstrated that protein kinase A (PKA)/KIN-1 in the neurons contributes to resistance against Salmonella enterica infection in C. elegans. Microarray analysis revealed that PKA/KIN-1 regulates the expression of a set of antimicrobial effectors in the non-neuron tissues, which are required for innate immune responses to S. enterica. Furthermore, PKA/KIN-1 regulated the expression of lysosomal genes during S. enterica infection. Our results suggest that the lysosomal signaling molecules are involved in autophagy by controlling autophagic flux, rather than formation of autophagosomes. As autophagy is crucial for host defense against S. enterica infection in a metazoan, the lysosomal pathway also acts as a downstream effector of the PKA/KIN-1 signaling for innate immunity. Our data indicate that the PKA pathway contributes to innate immunity in C. elegans by signaling from the nervous system to periphery tissues to protect the host against pathogens.
秀丽隐杆线虫是一种可遗传的模式生物，非常适合用于研究宿主固有免疫。尽管与病原体接触的秀丽隐杆线虫的肠道和表皮可能是免疫功能的作用部位，但最近的研究表明，神经系统可以控制秀丽隐杆线虫的固有免疫。在本报告中，我们证明了神经元中的蛋白激酶 A（PKA）/KIN-1 有助于秀丽隐杆线虫抵抗沙门氏菌感染。微阵列分析显示，PKA/KIN-1 调节非神经元组织中一组抗菌效应物的表达，这些效应物是对沙门氏菌固有免疫反应所必需的。此外，PKA/KIN-1 在沙门氏菌感染过程中调节溶酶体基因的表达。我们的结果表明，溶酶体信号分子通过控制自噬通量参与自噬，而不是自噬体的形成。由于自噬对于宿主抵抗沙门氏菌感染至关重要，因此溶酶体途径也是 PKA/KIN-1 信号通路用于固有免疫的下游效应物。我们的数据表明，PKA 途径通过从神经系统向周围组织发出信号来参与秀丽隐杆线虫的固有免疫，以保护宿主免受病原体的侵害。
