Valadares Diogo Garcia, Clay Owen Scott, Chen Yani, Scorza Breanna Mary, Cassel Suzanne Louise, Sutterwala Fayyaz Shiraz, Wilson Mary Edythe
Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Department of Pediatrics, Division of Pediatric Rheumatology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA.
iScience. 2023 Feb 8;26(3):106163. doi: 10.1016/j.isci.2023.106163. eCollection 2023 Mar 17.
The NLR protein NLRP12 contributes to innate immunity, but the mechanism remains elusive. Infection of or wild-type mice with led to aberrant parasite tropism. Parasites replicated to higher levels in livers of mice than in the livers of WT mice and failed to disseminate to spleens. Most retained liver parasites resided in dendritic cells (DCs), with correspondingly fewer infected DCs in spleens. Furthermore, DCs expressed lower CCR7 than WT DCs, failed to migrate toward CCL19 or CCL21 in chemotaxis assays, and migrated poorly to draining lymph nodes after sterile inflammation. -infected DCs were significantly less effective at transporting parasites to lymph nodes than WT DCs. Consistently, adaptive immune responses were also impaired in infected mice. We hypothesize that -expressing DCs are required for efficient dissemination and immune clearance of from the site of initial infection. This is at least partly due to the defective expression of CCR7.
NLR蛋白NLRP12有助于先天免疫，但其机制仍不清楚。用……感染……或野生型小鼠会导致异常的寄生虫嗜性。寄生虫在……小鼠肝脏中的复制水平高于野生型小鼠肝脏，且无法扩散到脾脏。大多数滞留于肝脏的寄生虫存在于树突状细胞（DCs）中，相应地，脾脏中被感染的DCs较少。此外，……DCs表达的CCR7低于野生型DCs，在趋化性试验中未能向CCL19或CCL21迁移，并且在无菌炎症后向引流淋巴结的迁移能力较差。感染……的……DCs在将寄生虫转运至淋巴结方面明显不如野生型DCs有效。同样，感染……的小鼠的适应性免疫反应也受到损害。我们推测，表达……的DCs对于从初始感染部位有效传播和免疫清除……是必需的。这至少部分是由于CCR7的表达缺陷。
