Institut Pasteur de Lille, Center for Infection and Immunity of Lille, Lille, France.
PLoS One. 2012;7(8):e41952. doi: 10.1371/journal.pone.0041952. Epub 2012 Aug 7.
Scavenger receptors and Toll-like receptors (TLRs) cooperate in response to danger signals to adjust the host immune response. The TLR3 agonist double stranded (ds)RNA is an efficient activator of innate signalling in bronchial epithelial cells. In this study, we aimed at defining the role played by scavenger receptors expressed by bronchial epithelial cells in the control of the innate response to dsRNA both in vitro and in vivo. Expression of several scavenger receptor involved in pathogen recognition was first evaluated in human bronchial epithelial cells in steady-state and inflammatory conditions. Their implication in the uptake of dsRNA and the subsequent cell activation was evaluated in vitro by competition with ligand of scavenger receptors including maleylated ovalbumin and by RNA silencing. The capacity of maleylated ovalbumin to modulate lung inflammation induced by dsRNA was also investigated in mice. Exposure to tumor necrosis factor-α increased expression of the scavenger receptors LOX-1 and CXCL16 and the capacity to internalize maleylated ovalbumin, whereas activation by TLR ligands did not. In contrast, the expression of SR-B1 was not modulated in these conditions. Interestingly, supplementation with maleylated ovalbumin limited dsRNA uptake and inhibited subsequent activation of bronchial epithelial cells. RNA silencing of LOX-1 and SR-B1 strongly blocked the dsRNA-induced cytokine production. Finally, administration of maleylated ovalbumin in mice inhibited the dsRNA-induced infiltration and activation of inflammatory cells in bronchoalveolar spaces and lung draining lymph nodes. Together, our data characterize the function of SR-B1 and LOX-1 in bronchial epithelial cells and their implication in dsRNA-induced responses, a finding that might be relevant during respiratory viral infections.
清道夫受体和 Toll 样受体 (TLRs) 通过合作对危险信号做出反应，以调整宿主的免疫反应。TLR3 激动剂双链 (ds) RNA 是支气管上皮细胞固有信号的有效激活剂。在这项研究中，我们旨在确定支气管上皮细胞表达的清道夫受体在控制 dsRNA 诱导的固有反应中的作用，包括在体外和体内。首先在稳态和炎症条件下评估了几种参与病原体识别的清道夫受体在人支气管上皮细胞中的表达。通过与清道夫受体配体（包括马来酰化卵清蛋白）竞争和 RNA 沉默，评估了它们在摄取 dsRNA 和随后的细胞激活中的作用。还研究了马来酰化卵清蛋白在调节 dsRNA 诱导的肺部炎症中的作用。肿瘤坏死因子-α 的暴露增加了清道夫受体 LOX-1 和 CXCL16 的表达和对马来酰化卵清蛋白的内化能力，而 TLR 配体的激活则没有。相反，在这些条件下，SR-B1 的表达没有被调节。有趣的是，补充马来酰化卵清蛋白限制了 dsRNA 的摄取并抑制了随后的支气管上皮细胞激活。LOX-1 和 SR-B1 的 RNA 沉默强烈阻断了 dsRNA 诱导的细胞因子产生。最后，在小鼠中给予马来酰化卵清蛋白抑制了 dsRNA 诱导的支气管肺泡空间和肺引流淋巴结中炎症细胞的浸润和激活。总之，我们的数据描述了 SR-B1 和 LOX-1 在支气管上皮细胞中的功能及其在 dsRNA 诱导反应中的作用，这一发现可能与呼吸道病毒感染有关。
