Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli (CERELA-CONICET), Tucuman, Argentina.
Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
Front Immunol. 2020 Sep 29;11:568636. doi: 10.3389/fimmu.2020.568636. eCollection 2020.
The oral administration of CRL1505 differentially modulates the respiratory innate antiviral immune response triggered by Toll-like receptor 3 (TLR3) activation in infant mice, improving the resistance to Respiratory Syncytial Virus (RSV) infection. In this work, by using macrophages depletion experiments and a detailed study of their production of cytokines and antiviral factors we clearly demonstrated the key role of this immune cell population in the improvement of both viral elimination and the protection against lung tissue damage induced by the CRL1505 strain. Orally administered CRL1505 activated alveolar macrophages and enhanced their ability to produce type I interferons (IFNs) and IFN-γ in response to RSV infection. Moreover, an increased expression of , and was observed in alveolar macrophages after the oral treatment with CRL1505, which was consistent with the enhanced RSV clearance. The depletion of alveolar macrophages by the time of CRL1505 administration abolished the ability of infant mice to produce increased levels of IL-10 in response to RSV infection. However, no improvement in IL-10 production was observed when primary cultures of alveolar macrophages obtained from CRL1505-treated mice were analyzed. Of note, alveolar macrophages from the CRL1505 group had an increased production of IL-6 and IL-27 suggesting that these cells may play an important role in limiting inflammation and protecting lung function during RSV infection, by increasing the maturation and activation of Treg cells and their subsequent production of IL-10. In addition, we provided evidence of the important role of CD4 cells and IFN-γ in the activation of alveolar macrophages highlighting a putative pathway through which the intestinal and respiratory mucosa are communicated under the influence of CRL1505.
口服 CRL1505 可调节 Toll 样受体 3 (TLR3) 激活引发的婴幼儿鼠呼吸先天抗病毒免疫反应，提高对呼吸道合胞病毒 (RSV) 感染的抵抗力。在这项工作中，通过使用巨噬细胞耗竭实验和对其细胞因子和抗病毒因子产生的详细研究，我们清楚地证明了这种免疫细胞群在改善病毒消除和保护肺部组织免受 CRL1505 株损伤方面的关键作用。口服给予 CRL1505 可激活肺泡巨噬细胞，并增强其在 RSV 感染时产生 I 型干扰素 (IFN) 和 IFN-γ 的能力。此外，在口服 CRL1505 治疗后，肺泡巨噬细胞中观察到 、 和 的表达增加，这与 RSV 清除增强一致。在给予 CRL1505 的时间耗竭肺泡巨噬细胞会消除婴幼儿鼠在 RSV 感染时产生增加的 IL-10 水平的能力。然而，当分析来自 CRL1505 处理小鼠的原代肺泡巨噬细胞培养物时，未观察到 IL-10 产生的改善。值得注意的是，来自 CRL1505 组的肺泡巨噬细胞产生更多的 IL-6 和 IL-27，表明这些细胞可能通过增加 Treg 细胞的成熟和激活及其随后产生的 IL-10，在 RSV 感染期间限制炎症和保护肺功能方面发挥重要作用。此外，我们提供了证据证明 CD4 细胞和 IFN-γ 在肺泡巨噬细胞激活中的重要作用，突出了肠道和呼吸道黏膜在 CRL1505 影响下进行交流的潜在途径。
