Cátedra de Inmunología, Instituto de Microbiología, Facultad de Bioquímica, Química y Farmacia, UNT, Ayacucho 471, 4000 Tucumán, Argentina.
Instituto de Medicina Molecular y Celular Aplicada 'IMMCA', Dorrego 1080, 4000 Tucumán, Argentina.
Benef Microbes. 2020 Dec 2;11(8):767-778. doi: 10.3920/BM2020.0055.
This study is based on our previous research showing that commercial probiotic fermented milk (PFM) intake mitigates respiratory allergy development to ovalbumin (OVA) in adult mice (6-weeks old) increasing specific immunoglobulin (Ig)G2a and interferon (IFN)-γ rather than IgE. The aim was to determine if PFM exerts a protective effect when an allergy model is induced 5 days after weaning and whether the mechanisms involved are similar to those previously reported. Before inducing allergy, a group of 21-day old BALB/c mice received PFM for 10 days to analyse the impact on intestinal epithelial cells (IECs) activation. Two more groups received PFM for 5 days and were sensitised with OVA; only one group continued taking PFM until the end of the experiment. Sensitisation scheme: 3 OVA injections 1% in phosphate buffered saline (PBS) plus 7 days OVA aerosol exposure and re-stimulus 15 days later. The contents of specific- IgE, IgG, total-secretory-IgA and Th1/Th2 balance in serum, bronchoalveolar lavage (BAL) and gut were measured at 7 and 15 days post-sensitisation (dPS) and 2 days post-re-stimulus (2dPR). Treg cells in lungs were also quantified. Results were compared with normal and sensitised controls. PFM induced mild activation of IECs increasing monocyte chemoattractant protein-1 (MCP-1 or CCL2) and interleukin (IL)-6 production. In sensitised mice, PFM controlled the response inducing IgG rather than IgE at 7 and 15-dPS and 2dPR (60 days old). Th1-balance (IFN-γ) was favoured by PFM in lungs at 7 dPS with low levels of IL-10 released to regulate the response. Total-S-IgA increased in lungs and gut; however, PFM intake did not affect Treg cells in lungs. PFM maintains controlled stimulation of the immune cells involved in Th1 response, favouring IgG at the respiratory mucosal site. Although the effect was not as strong as that reported previously, PFM promoted maturation and activation of gut immune cells preserving intestinal homeostasis and lung immune response.
本研究基于我们之前的研究结果，即商业益生菌发酵乳（PFM）的摄入可减轻成年小鼠（6 周龄）对卵清蛋白（OVA）的呼吸道过敏发展，增加特异性免疫球蛋白（Ig）G2a 和干扰素（IFN）-γ，而不是 IgE。本研究的目的是确定 PFM 是否在断奶后 5 天诱导过敏模型时发挥保护作用，以及所涉及的机制是否与之前报道的相似。在诱导过敏之前，一组 21 天大的 BALB/c 小鼠接受 PFM 治疗 10 天，以分析其对肠上皮细胞（IEC）激活的影响。另外两组小鼠接受 PFM 治疗 5 天，并用 OVA 致敏；只有一组继续服用 PFM 直到实验结束。致敏方案：3 次 OVA 注射（1%磷酸盐缓冲盐水（PBS）），加 7 天 OVA 雾化暴露，15 天后再刺激。在致敏后 7 天和 15 天（dPS）以及再刺激后 2 天（2dPR）时，测量血清、支气管肺泡灌洗液（BAL）和肠道中特异性 IgE、IgG、总分泌型 IgA 和 Th1/Th2 平衡的含量，并定量测定肺部 Treg 细胞。将结果与正常和致敏对照组进行比较。PFM 轻度激活 IEC，增加单核细胞趋化蛋白-1（MCP-1 或 CCL2）和白细胞介素（IL）-6 的产生。在致敏小鼠中，PFM 在 7 和 15-dPS 以及 2dPR（60 天大）时控制反应，诱导 IgG 而不是 IgE。PFM 在 7-dPS 时促进肺部 Th1 平衡（IFN-γ），同时释放低水平的 IL-10 以调节反应。总-S-IgA 在肺部和肠道增加；然而，PFM 摄入并不影响肺部的 Treg 细胞。PFM 维持参与 Th1 反应的免疫细胞的受控刺激，在呼吸道黏膜部位促进 IgG 的产生。尽管效果不如之前报道的那么强，但 PFM 促进了肠道免疫细胞的成熟和激活，维持了肠道内稳态和肺部免疫反应。
