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

140 Citations (Scopus)

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

Fingerprint

Toll-Like Receptor 7
Interleukin-23
West Nile virus
Encephalitis
Virus Diseases
Interleukin-12
Interleukin-23 Subunit p19
Interleukin-12 Subunit p35
Myeloid Differentiation Factor 88
Macrophages
RNA
Flavivirus
Viremia
Culicidae
Leukocytes
Cytokines

Keywords

  • CELLIMMUNO
  • HUMDISEASE

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing. / Town, Terrence; Bai, Fengwei; Wang, Tian; Kaplan, Amber T.; Qian, Feng; Montgomery, Ruth R.; Anderson, John F.; Flavell, Richard A.; Fikrig, Erol.

In: Immunity, Vol. 30, No. 2, 20.02.2009, p. 242-253.

Research output: Contribution to journalArticle

Town, T, Bai, F, Wang, T, Kaplan, AT, Qian, F, Montgomery, RR, Anderson, JF, Flavell, RA & Fikrig, E 2009, 'Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing', Immunity, vol. 30, no. 2, pp. 242-253. https://doi.org/10.1016/j.immuni.2008.11.012
Town, Terrence ; Bai, Fengwei ; Wang, Tian ; Kaplan, Amber T. ; Qian, Feng ; Montgomery, Ruth R. ; Anderson, John F. ; Flavell, Richard A. ; Fikrig, Erol. / Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing. In: Immunity. 2009 ; Vol. 30, No. 2. pp. 242-253.
@article{f083e9b4c7144f2ba3270c5f0f1921c8,
title = "Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing",
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.",
keywords = "CELLIMMUNO, HUMDISEASE",
author = "Terrence Town and Fengwei Bai and Tian Wang and Kaplan, {Amber T.} and Feng Qian and Montgomery, {Ruth R.} and Anderson, {John F.} and Flavell, {Richard A.} and Erol Fikrig",
year = "2009",
month = "2",
day = "20",
doi = "10.1016/j.immuni.2008.11.012",
language = "English (US)",
volume = "30",
pages = "242--253",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Toll-like Receptor 7 Mitigates Lethal West Nile Encephalitis via Interleukin 23-Dependent Immune Cell Infiltration and Homing

AU - Town, Terrence

AU - Bai, Fengwei

AU - Wang, Tian

AU - Kaplan, Amber T.

AU - Qian, Feng

AU - Montgomery, Ruth R.

AU - Anderson, John F.

AU - Flavell, Richard A.

AU - Fikrig, Erol

PY - 2009/2/20

Y1 - 2009/2/20

N2 - 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.

AB - 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.

KW - CELLIMMUNO

KW - HUMDISEASE

UR - http://www.scopus.com/inward/record.url?scp=60149109538&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60149109538&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2008.11.012

DO - 10.1016/j.immuni.2008.11.012

M3 - Article

VL - 30

SP - 242

EP - 253

JO - Immunity

JF - Immunity

SN - 1074-7613

IS - 2

ER -