Adel-Patient K, Ah-Leung S, Creminon C, Nouaille S, Chatel J-M, Langella P, Wal J-M
Unité d'Immuno-Allergie Alimentaire, INRA/CEA, CEA de Saclay, Gif-sur-Yvette, France.
Clin Exp Allergy. 2005 Apr;35(4):539-46. doi: 10.1111/j.1365-2222.2005.02225.x.
The use of probiotics such as Lactococcus lactis and other lactic acid bacteria (LAB) has been proposed for the management of food allergy. However, no experimental study has clearly demonstrated any preventive or therapeutic inhibition of an allergen-specific IgE response.
We aimed to study the immunomodulatory effect of recombinant L. lactis expressing bovine beta-lactoglobulin (BLG), a major cow's milk allergen, in a validated mouse model of allergy.
Six-week-old female Balb/c mice received five repeated doses of BLG, of L. lactis plus BLG, or of recombinant L. lactis by gavage. Different recombinant strains were inoculated, which corresponded to BLG doses ranging from 4 to 70 microg/mice. Mice were then sensitized by intra-peritoneal injection of BLG emulsified in incomplete Freund's adjuvant to induce high IgE concentrations.
Pre-treatment with natural L. lactis plus BLG allowed induction of BLG-specific T-helper type 1 (Th1) response, and abrogated the oral tolerance induced by BLG alone, demonstrating the adjuvant effect of this non-colonizing LAB. Moreover, pre-treatment with some of the recombinant strains favoured the development of a Th1 response inhibiting the Th2 one: it induced a significant decrease of specific IgE response, and an intense increase of specific IgG2a and IFN-gamma productions. The most efficient strains that inhibited the IgE response were those producing the highest amounts of the BLG protein.
Oral administration of some recombinant L. lactis was demonstrated to induce a specific Th1 response down-regulating a further Th2 one. Prophylaxis protocols will thus be evaluated using the most efficient strains.
已有人提出使用乳酸乳球菌等益生菌及其他乳酸菌(LAB)来管理食物过敏。然而,尚无实验研究能明确证明对过敏原特异性IgE反应有任何预防或治疗性抑制作用。
我们旨在研究表达牛β-乳球蛋白(BLG,一种主要的牛奶过敏原)的重组乳酸乳球菌在经过验证的小鼠过敏模型中的免疫调节作用。
六周龄雌性Balb/c小鼠通过灌胃接受五剂重复剂量的BLG、乳酸乳球菌加BLG或重组乳酸乳球菌。接种了不同的重组菌株,其对应的BLG剂量范围为4至70微克/小鼠。然后通过腹腔注射不完全弗氏佐剂乳化的BLG使小鼠致敏,以诱导高浓度的IgE。
用天然乳酸乳球菌加BLG进行预处理可诱导BLG特异性1型辅助性T细胞(Th1)反应,并消除单独使用BLG诱导的口服耐受性,证明了这种非定植LAB的佐剂作用。此外,用一些重组菌株进行预处理有利于Th1反应的发展,从而抑制Th2反应:它导致特异性IgE反应显著降低,特异性IgG₂a和干扰素-γ产生强烈增加。抑制IgE反应最有效的菌株是那些产生BLG蛋白量最高的菌株。
已证明口服某些重组乳酸乳球菌可诱导特异性Th1反应,进而下调Th2反应。因此,将使用最有效的菌株评估预防方案。