Departamento de Ciencias Biológicas, Instituto de Estudios Inmunológicos y Fisiopatológicos (IIFP), UNLP, CONICET, asociado a CIC PBA, Facultad de Ciencias Exactas, La Plata, Argentina.
Instituto de Investigaciones Biotecnológicas, Dr. Rodolfo A. Ugalde (IIB-INTECH), CONICET, Universidad Nacional de San Martín, Buenos Aires, Argentina.
Front Immunol. 2021 Apr 30;12:641597. doi: 10.3389/fimmu.2021.641597. eCollection 2021.
The intestinal mucosa is lined by epithelial cells, which are key cells to sustain gut homeostasis. Food allergy is an immune-mediated adverse reaction to food, likely due to defective regulatory circuits. is a non-pathogenic bacterium with immunomodulatory properties. We hypothesize that the anti-inflammatory effect of dead . on activated epithelial cells modulates milk allergy through the restoration of tolerance in a mouse model. Epithelial cells (Caco-2 and enterocytes from mouse gut) and macrophages were stimulated with . and induction of luciferase under the NF-κB promoter, ROS and cytokines production were studied. Balb/c mice were mucosally sensitized with cow´s milk proteins plus cholera toxin and orally challenged with the allergen to evidence hypersensitivity symptoms. After that, mice were orally administered with heat-killed . as treatment and then challenged with the allergen. The therapeutic efficacy was (clinical score and cutaneous test) and (serum specific antibodies and cytokines-ELISA, and cell analysis-flow cytometry) evaluated. Heat-killed . modulated the induction of pro-inflammatory chemokines, with an increase in anti-inflammatory cytokines by intestinal epithelial cells and by macrophages with decreased OX40L expression. , oral administration of . increased the frequency of lamina propria CD4CD25FoxP3 T cells, and clinical signs were lower in . -treated mice compared with milk-sensitized animals. depletion of Tregs (anti-CD25) abrogated . immunomodulation. In conclusion, these bacteria suppressed the intestinal inflammatory immune response to reverse food allergy.
肠黏膜由上皮细胞组成，这些细胞是维持肠道内稳态的关键细胞。食物过敏是一种针对食物的免疫介导的不良反应，可能是由于调节回路缺陷所致。 是一种具有免疫调节特性的非致病性细菌。我们假设，死亡的 对激活的上皮细胞的抗炎作用通过在小鼠模型中恢复耐受性来调节牛奶过敏。用 刺激上皮细胞（Caco-2 和来自小鼠肠道的肠细胞）和巨噬细胞，并研究 NF-κB 启动子下的荧光素酶诱导、ROS 和细胞因子产生。用牛乳蛋白加霍乱毒素对 Balb/c 小鼠进行黏膜致敏，并口服过敏原以证明过敏症状。之后，用热灭活的 对小鼠进行口服治疗，然后用过敏原进行挑战。治疗效果评估如下：（临床评分和皮肤测试）和 （血清特异性抗体和细胞因子-ELISA，以及细胞分析-流式细胞术）。热灭活的 调节了促炎趋化因子的诱导，同时增加了肠道上皮细胞和巨噬细胞中抗炎细胞因子的表达，降低了 OX40L 的表达。此外，口服 增加了固有层 CD4CD25FoxP3 T 细胞的频率，与牛奶致敏动物相比， 处理的小鼠临床症状较低。Treg（抗-CD25）耗竭消除了 的免疫调节作用。总之，这些细菌抑制了肠道炎症免疫反应，从而逆转了食物过敏。
