Laboratory of Immunobiotechnology, Reference Centre for Lactobacilli, (CERELA-CONICET), Tucuman 4000, Argentina.
Food and Feed Immunology Group, Laboratory of Animal Products Chemistry, Graduate School of Agricultural Science, Tohoku University, Sendai 980-8572, Japan.
Cells. 2020 Jul 9;9(7):1653. doi: 10.3390/cells9071653.
The nasal priming with nonviable CRL1505 (NV1505) or its purified peptidoglycan (PG1505) differentially modulates the respiratory innate immune response in infant mice, improving their resistance to primary respiratory syncytial virus (RSV) infection and secondary pneumococcal pneumonia. In association with the protection against RSV-pneumococcal superinfection, it was found that NV1505 or PG1505 significantly enhance the numbers of CD11cSiglecF alveolar macrophages (AMs) producing interferon (IFN)-β. In this work, we aimed to further advance in the characterization of the beneficial effects of NV1505 and PG1505 in the context of a respiratory superinfection by evaluating whether their immunomodulatory properties are dependent on AM functions. Macrophage depletion experiments and a detailed study of their production of cytokines and antiviral factors clearly demonstrated the key role of this immune cell population in the improvement of both the reduction of pathogens loads and the protection against lung tissue damage induced by the immunobiotic CRL1505 strain. Studies at basal conditions during primary RSV or infections, as well as during secondary pneumococcal pneumonia, brought the following five notable findings regarding the immunomodulatory effects of NV1505 and PG1505: (a) AMs play a key role in the beneficial modulation of the respiratory innate immune response and protection against RSV infection, (b) AMs are necessary for improved protection against primary and secondary pneumococcal pneumonia, (c) the generation of activated/trained AMs would be essential for the enhanced protection against respiratory pathogens, (d) other immune and nonimmune cell populations in the respiratory tract may contribute to the protection against bacterial and viral infections, and (e) the immunomodulatory properties of NV1505 and PG1505 are strain-specific. These findings significantly improve our knowledge about the immunological mechanisms involved in the modulation of respiratory immunity induced by beneficial microbes.
用非存活的 CRL1505（NV1505）或其纯化的肽聚糖（PG1505）对婴儿小鼠进行鼻腔预处理，可调节呼吸固有免疫反应，提高其对原发呼吸道合胞病毒（RSV）感染和继发肺炎链球菌性肺炎的抵抗力。与对 RSV-肺炎链球菌混合感染的保护作用相关，发现 NV1505 或 PG1505 可显著增加产生干扰素（IFN）-β的 CD11cSiglecF 肺泡巨噬细胞（AMs）的数量。在这项工作中，我们旨在通过评估其免疫调节特性是否依赖于 AM 功能，进一步深入研究 NV1505 和 PG1505 在呼吸混合感染背景下的有益作用。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清楚地表明，这种免疫细胞群体在改善 CRL1505 菌株减少病原体负荷和保护肺组织免受损伤方面发挥着关键作用。在原发 RSV 或 感染以及继发肺炎链球菌性肺炎的基础条件下进行的研究带来了以下关于 NV1505 和 PG1505 的免疫调节作用的五个显著发现：（a）AMs 在调节呼吸固有免疫反应和保护 RSV 感染方面发挥着关键作用，（b）AMs 是改善对原发和继发肺炎链球菌性肺炎保护作用所必需的，（c）激活/训练的 AMs 的产生对于增强对呼吸道病原体的保护作用至关重要，（d）呼吸道中的其他免疫和非免疫细胞群体可能有助于对细菌和病毒感染的保护，以及（e）NV1505 和 PG1505 的免疫调节特性是菌株特异性的。这些发现显著提高了我们对有益微生物诱导的呼吸免疫调节中涉及的免疫机制的认识。
