The role of Toll-like receptor 4 versus interleukin-12 in immunity to respiratory syncytial virus
The role of Toll-like receptor 4 versus interleukin-12 in immunity to respiratory syncytial virus
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DOI：
10.1002/eji.200324449
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发表时间：
2004-04-01
影响因子：
5.4
通讯作者：
Freudenberg, M
中科院分区：
文献类型：
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作者：
Ehl, S;Bischoff, R;Freudenberg, M
Toll样受体（TLR）和IL-12代表先天免疫的关键要素。使用C57 BL/10 ScCr小鼠，显示TLR 4对于控制呼吸道合胞病毒（RSV）感染是重要的。由于这些小鼠在IL-12 R中具有额外的缺陷，我们重新研究了缺乏功能性TLR 4、功能性IL-12-IL-12 R相互作用或两者的几种C57 BL/10和BALB/c小鼠品系对RSV的免疫力。在没有功能性IL-12轴的情况下，C57 BL/10小鼠的早期病毒控制受损，但在BALB/c小鼠中未受损。相比之下，TLR 4对RSV消除没有影响。在IL-12缺陷型BALB/c小鼠中，肺NK细胞募集受损，在两种遗传背景的IL-12/IL-12 R缺陷型小鼠中，NK细胞毒性降低。TLR 4的缺乏对NK细胞的募集或NK活性没有影响，也对其他肺部炎症细胞的募集没有影响。RSV特异性T细胞免疫的激活，包括T细胞介导的免疫病理学，在所有突变株中是正常的。这些发现清楚地反驳了TLR 4的重要作用，并定义了IL-12在原发性鼠RSV感染中的有限作用。
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.