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

Authors :
Zhu, Kai
Yang, Juhao
Luo, Kaiming
Yang, Chunhui
Zhang, Na
Xu, Ruifeng
Chen, Jianxia
Jin, Mingfei
Xu, Bin
Guo, Nining
Wang, Jianrong
Chen, Zuolong
Cui, Ying
Zhao, Hui
Wang, Yan
Deng, Chaoyang
Bai, Li
Ge, Baoxue
Qin, Cheng-Feng
Shen, Hao
Source :
PLoS Pathogens. Jan2015, Vol. 11 Issue 1, p1-19. 19p.
Publication Year :
2015

Abstract

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

Details

Language :
English
ISSN :
15537366
Volume :
11
Issue :
1
Database :
Academic Search Index
Journal :
PLoS Pathogens
Publication Type :
Academic Journal
Accession number :
100763408
Full Text :
https://doi.org/10.1371/journal.ppat.1004613