Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing

作者：Town Terrence; Bai Fengwei; Wang Tian; Kaplan Amber T; Qian Feng; Montgomery Ruth R; Anderson John F; Flavell Richard A^*; Fikrig Erol

来源：Immunity, 2009, 30(2): 242-253.

DOI：10.1016/j.immuni.2008.11.012

West Nile virus (WNV), a mosquito-transmitted single-stranded RNA (ssRNA) flavivirus, causes human disease of variable severity. We investigated Toll-like receptor 7-deficient (TLr7(-/-)) and myeloid differentiation factor 88-deficient (Myd88(-/-)) mice, which both have defective recognition of ssRNA, and found increased viremia. and susceptibility to lethal WNV infection. Despite increased tissue concentrations of most innate cytokines, CD45( ) leukocytes and CD11b( ) macrophages failed to home to WNV-infected cells and infiltrate into target organs of Tlr7(-/-) mice. Tlr7(-/-) mice and macrophages had reduced interleukin-12 (IL-12) and IL-23 responses after WNV infection, and mice deficient in IL-12 p40 and IL-23 p40 (II12b(-/)) or IL-23 p19 (II23a(-/)), but not IL-12 p35 (II12a(-/)), responded similarly to Tlr7(-/) mice, with increased susceptibility to lethal WNV encephalitis. Collectively, these results demonstrate that TLR7 and IL-23-dependent WNV responses represent a vital host defense mechanism that operates by affecting immune cell homing to infected target cells.

• 出版日期2009-2-20