Murawski Matthew R, Bowen Glennice N, Cerny Anna M, Anderson Larry J, Haynes Lia M, Tripp Ralph A, Kurt-Jones Evelyn A, Finberg Robert W
Department of Medicine, University of Massachusetts Medical Center, 364 Plantation Street, Lazare Research Building, Worcester, Massachusetts 01605, USA.
J Virol. 2009 Feb;83(3):1492-500. doi: 10.1128/JVI.00671-08. Epub 2008 Nov 19.
Respiratory syncytial virus (RSV) is a common cause of infection that is associated with a range of respiratory illnesses, from common cold-like symptoms to serious lower respiratory tract illnesses such as pneumonia and bronchiolitis. RSV is the single most important cause of serious lower respiratory tract illness in children <1 year of age. Host innate and acquired immune responses activated following RSV infection have been suspected to contribute to RSV disease. Toll-like receptors (TLRs) activate innate and acquired immunity and are candidates for playing key roles in the host immune response to RSV. Leukocytes express TLRs, including TLR2, TLR6, TLR3, TLR4, and TLR7, that can interact with RSV and promote immune responses following infection. Using knockout mice, we have demonstrated that TLR2 and TLR6 signaling in leukocytes can activate innate immunity against RSV by promoting tumor necrosis factor alpha, interleukin-6, CCL2 (monocyte chemoattractant protein 1), and CCL5 (RANTES). As previously noted, TLR4 also contributes to cytokine activation (L. M. Haynes, D. D. Moore, E. A. Kurt-Jones, R. W. Finberg, L. J. Anderson, and R. A. Tripp, J. Virol. 75:10730-10737, 2001, and E. A. Kurt-Jones, L. Popova, L. Kwinn, L. M. Haynes, L. P. Jones, R. A. Tripp, E. E. Walsh, M. W. Freeman, D. T. Golenbock, L. J. Anderson, and R. W. Finberg, Nat. Immunol. 1:398-401, 2000). Furthermore, we demonstrated that signals generated following TLR2 and TLR6 activation were important for controlling viral replication in vivo. Additionally, TLR2 interactions with RSV promoted neutrophil migration and dendritic cell activation within the lung. Collectively, these studies indicate that TLR2 is involved in RSV recognition and subsequent innate immune activation.
呼吸道合胞病毒（RSV）是一种常见的感染病原体，与一系列呼吸道疾病相关，从类似普通感冒的症状到严重的下呼吸道疾病，如肺炎和细支气管炎。RSV是1岁以下儿童严重下呼吸道疾病的最重要单一病因。RSV感染后激活的宿主固有免疫和获得性免疫反应被怀疑与RSV疾病的发生有关。Toll样受体（TLR）激活固有免疫和获得性免疫，是在宿主对RSV的免疫反应中发挥关键作用的候选者。白细胞表达TLR，包括TLR2、TLR6、TLR3、TLR4和TLR7，它们可与RSV相互作用并在感染后促进免疫反应。利用基因敲除小鼠，我们已经证明白细胞中的TLR2和TLR6信号传导可通过促进肿瘤坏死因子α、白细胞介素-6、CCL2（单核细胞趋化蛋白1）和CCL5（调节激活正常T细胞表达和分泌因子）来激活针对RSV的固有免疫。如前所述，TLR4也有助于细胞因子的激活（L.M.海恩斯、D.D.摩尔、E.A.库尔特-琼斯、R.W.芬伯格、L.J.安德森和R.A.特里普，《病毒学杂志》75:10730-10737，2001年；以及E.A.库尔特-琼斯、L.波波娃、L.奎恩、L.M.海恩斯、L.P.琼斯、R.A.特里普、E.E.沃尔什、M.W.弗里曼、D.T.戈伦博克、L.J.安德森和R.W.芬伯格，《自然免疫学》1:398-401，2000年）。此外，我们证明了TLR2和TLR6激活后产生的信号对于控制体内病毒复制很重要。另外，TLR2与RSV的相互作用促进了肺内中性粒细胞的迁移和树突状细胞的激活。总的来说，这些研究表明TLR2参与了RSV的识别及随后的固有免疫激活。
