Role of Natural Killer and Gamma-Delta T cells in West Nile Virus Infection

Wang, Tian; Welte, Thomas

There are few antigens reported to be recognized by γδ T cell receptors [79] . TLRs sense different pathogen-associated molecular patterns (PAMP) during microbial infection [80, 81] . The expression of PRRs, such as TLR2, TLR3, TLR4, and TLR7/8, on  T cells has been reported [82] [83] [84] [85] . Among them, TLR3-and TLR7-induced innate cytokine responses are involved in both protection and pathogenesis during WNV infection [72, [86] [87] [88] . Myeloid differentiation factor 88 (MyD88), the primary adaptor for most TLRs, also restricts WNV by inhibiting replication in subsets of cells and modulating immune cell migration into the CNS [89] . We have recently found that  T cells of MyD88 and TLR -deficient mice, had a reduced expansion and activation compared to those of wild-type mice following WNV infection, which indicates a role of MyD88-dependent PRR signaling in ï§ï¤ï€ T cell activation [90] . TLRs are known to directly or indirectly contribute to  T cell activation. TLR ligands could act as co-stimulatory signals for TCR-activated human  T cells [91, 92] . Alternatively,  T cells and DCs also exert regulatory influences on each other. For example, induction of human  T cells by poly I:C, a ligand for TLR3, depends on DCs mediated by Type-1 IFNs [93] . Human  T cells were activated by plasmacytoid DCs upon infection by another important flavivivirus, yellow fever virus [94] . Whether  T cells are induced by WNV directly via their innate immune receptors, such as TLRs, or indirectly by interaction with TLR-expressing innate immune cells remains under investigation.