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

Terrence Town, Fengwei Bai, Tian Wang, Amber T. Kaplan, Feng Qian, Ruth R. Montgomery, John F. Anderson, Richard A. Flavell, Erol Fikrig

Research output: Contribution to journalArticle

144 Scopus citations

Abstract

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 (Il12b-/-) or IL-23 p19 (Il23a-/-), but not IL-12 p35 (Il12a-/-), 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.

Original languageEnglish (US)
Pages (from-to)242-253
Number of pages12
JournalImmunity
Volume30
Issue number2
DOIs
StatePublished - Feb 20 2009
Externally publishedYes

Keywords

  • CELLIMMUNO
  • HUMDISEASE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Town, T., Bai, F., Wang, T., Kaplan, A. T., Qian, F., Montgomery, R. R., Anderson, J. F., Flavell, R. A., & Fikrig, E. (2009). Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing. Immunity, 30(2), 242-253. https://doi.org/10.1016/j.immuni.2008.11.012