鼠李糖乳杆菌 NCC2461 对围产期母鼠的干预可预防桦树花粉过敏的小鼠模型中的过敏炎症。

BACKGROUND: The hygiene hypothesis implies that microbial agents including probiotic bacteria may modulate foetal/neonatal immune programming and hence offer effective strategies for primary allergy prevention; however their mechanisms of action are poorly understood. We investigated whether oral administration of Lactobacillus paracasei NCC 2461 to mothers during gestation/lactation can protect against airway inflammation in offspring in a mouse model of birch pollen allergy, and examined the immune mechanisms involved. METHODS: BALB/c mice were treated daily with L. paracasei in drinking water or drinking water alone in the last week of gestation and during lactation. Their offspring were sensitized with recombinant Bet v 1, followed by aerosol challenge with birch pollen extract. RESULTS: Maternal exposure to L. paracasei prevented the development of airway inflammation in offspring, as demonstrated by attenuation of eosinophil influx in the lungs; reduction of IL-5 levels in bronchoalveolar lavage, and in lung and mediastinal lymph node cell cultures; and reduced peribronchial inflammatory infiltrate and mucus hypersecretion. While allergen-specific IgE and IgG antibody levels remained unchanged by the treatment, IL-4 and IL-5 production in spleen cell cultures were significantly reduced upon allergen stimulation in offspring of L. paracasei treated mice. Offspring of L. paracasei supplemented mothers had significantly reduced Bet v 1-specific as well as Concanavalin A-induced responses in spleen and mesenteric lymph node cell cultures, suggesting the modulation of both antigen-specific and mitogen-induced immune responses in offspring. These effects were associated with increased Foxp3 mRNA expression in the lungs and increased TGF-beta in serum. CONCLUSION: Our data show that in a mouse model of birch pollen allergy, perinatal administration of L. paracasei NCC 2461 to pregnant/lactating mothers protects against the development of airway inflammation in offspring by activating regulatory pathways, likely through TLR2/4 signalling.

背景：卫生假说表明，包括益生菌在内的微生物可以调节胎儿/新生儿的免疫编程，从而为初级过敏预防提供有效的策略；然而，其作用机制尚不清楚。我们研究了在桦树花粉过敏的小鼠模型中，母亲在妊娠/哺乳期口服副干酪乳杆菌 NCC 2461 是否可以预防后代的气道炎症，并研究了所涉及的免疫机制。

方法：BALB/c 小鼠在妊娠末期和哺乳期每天用 L. paracasei 处理饮用水或单独饮用水。它们的后代用重组 Bet v 1 致敏，然后用桦树花粉提取物进行气溶胶攻击。

结果：母体暴露于 L. paracasei 可预防后代气道炎症的发生，表现为肺部嗜酸性粒细胞浸润减少；支气管肺泡灌洗液以及肺和纵隔淋巴结细胞培养物中 IL-5 水平降低；以及减少周围支气管炎症浸润和粘液分泌过度。虽然治疗对过敏原特异性 IgE 和 IgG 抗体水平没有影响，但在 L. paracasei 处理小鼠后代的过敏原刺激下，脾细胞培养物中 IL-4 和 IL-5 的产生显著减少。L. paracasei 补充母亲的后代在脾和肠系膜淋巴结细胞培养物中对 Bet v 1 特异性和 Concanavalin A 诱导的反应均显著降低，提示调节了后代的抗原特异性和有丝分裂原诱导的免疫反应。这些作用与肺部 Foxp3 mRNA 表达增加和血清中 TGF-β增加有关。

结论：我们的数据表明，在桦树花粉过敏的小鼠模型中，在妊娠/哺乳期向母亲口服副干酪乳杆菌 NCC 2461 可通过激活调节途径，预防后代气道炎症的发生，可能通过 TLR2/4 信号通路。