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

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Enterovirus 71 (EV71) is a major causative pathogen of hand, foot and mouth disease. EV71 infection occurs mainly in children but rarely in adults. The factors that determine the susceptibility of children to EV71 infection remain elusive. Here, we found that the paucity of invariant natural killer T (iNKT) cells in new-born mice was associated with their susceptibility to EV71 infection. Furthermore, iNKT cells played a critical role in protecting older young mice from EV71 infection before their adaptive immune systems were fully developed. Mechanistically, TLR3 signaling in macrophages, but not in dendritic cells, was essentially required for iNKT cell activation during EV71 infection. Both interleukin (IL)-12 production and endogenous lipid antigens presented by macrophages were required for full iNKT cell activation. iNKT cells tended to prevent the dissemination of EV71 into central nervous system. Taken together, our findings provide a new insight into the susceptibility of children to EV71 infection, and imply that the manipulation of iNKT cells might represent a potential therapeutic strategy for HFMD and other viral infectious diseases in children.

Vyšlo v časopise: TLR3 Signaling in Macrophages Is Indispensable for the Protective Immunity of Invariant Natural Killer T Cells against Enterovirus 71 Infection. PLoS Pathog 11(1): e32767. doi:10.1371/journal.ppat.1004613
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004613

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