The role of Toll-like receptor 4 versus interleukin-12 in immunity to respiratory syncytial virus

被引:79
作者
Ehl, S
Bischoff, R
Ostler, T
Vallbracht, S
Schulte-Mönting, J
Poltorak, A
Freudenberg, M
机构
[1] Univ Freiburg, Childrens Hosp, D-79106 Freiburg, Germany
[2] Dept Med Biometry & Stat, Freiburg, Germany
[3] Max Planck Inst Immunobiol, Freiburg, Germany
关键词
Toll-like receptor; interleukin-12; virus; lung; innate immunity;
D O I
10.1002/eji.200324449
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Toll-like receptors (TLR) and IL-12 represent key elements of innate immunity. Using C57BL/10 ScCr mice it was shown that TLR4 is important for control of infection with respiratory syncytial virus (RSV). Since these mice have an additional defect in the IL-12R, we reinvestigated immunity to RSV in several C57BL/10 and BALB/c mouse strains lacking a functional TLR4, a functional IL-12-IL-12R interaction or both. In the absence of a functional IL-12 axis, early virus control was impaired in C57BL/10 mice, but not in BALB/c mice. By contrast, TLR4 had no impact on RSV elimination. Pulmonary NK cell recruitment was impaired in IL-12 deficient BALB/c mice and NK cytotoxicity was reduced in IL-12/IL-12R-deficient mice of both genetic backgrounds. Absence of TLR4 had no impact on NK cell recruitment or NK activity nor on recruitment of other pulmonary inflammatory cells. Activation of RSV-specific T cell immunity, including T cell mediated immunopathology, was normal in all mutant strains. These findings clearly argue against a significant role for TLR4 and define a limited role for IL-12 in primary murine RSV infection.
引用
收藏
页码:1146 / 1153
页数:8
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