TLR3 Signaling in Macrophages Is Indispensable for the Protective Immunity of Invariant Natural Killer T Cells against Enterovirus 71 Infection

• DOI: 10.1371/journal.ppat.1004613
• Publication Date: 2015-01-23T22:08:23Z
• Authors: Kai Zhu; Juhao Yang; Kaiming Luo; Chunhui Yang; Na Zhang; Ruifeng Xu; Jianxia Chen; Mingfei Jin; Bin Xu; Nining Guo; Jianrong Wang; Zuolong Chen; Ying Cui; Hui Zhao; Yan Wang; Chaoyang Deng; Li Bai; Baoxue Ge; Cheng-Feng Qin; Hao Shen; Chun-Fu Yang; Qibin Leng
• Keywords: CD1D; Enterovirus 71; TLR3

Enterovirus 71 (EV71) is the most virulent pathogen among enteroviruses that cause hand, foot and mouth disease in children but rarely adults. The mechanisms determine age-dependent susceptibility remain largely unclear. Here, we found paucity of invariant natural killer T (iNKT) cells together with immaturity immune system was related to neonatal mice EV71 infection. iNKT were crucial antiviral effector protect young from infection before their adaptive systems fully mature. led activation depending on signaling through TLR3 not other TLRs. Surprisingly, cell during required macrophages, dendritic (DCs). Mechanistically, interleukin (IL)-12 endogenous CD1d-restricted antigens both for full cells. Furthermore, CD1d-deficiency dramatically increased viral loads central nervous more severe EV71-infected mice. Altogether, our results suggest may be involved controlling when are developed, also imply might an intervention target treating patients.