Institute of Specific Prophylaxis and Tropical Medicine, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
PLoS One. 2012;7(7):e40271. doi: 10.1371/journal.pone.0040271. Epub 2012 Jul 6.
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.
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.
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.
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.
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。
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。
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。
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。
