Intranasal coadministration of live lactococci producing interleukin-12 and a major cow's milk allergen inhibits allergic reaction in mice
Intranasal coadministration of live lactococci producing interleukin-12 and a major cow's milk allergen inhibits allergic reaction in mice
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DOI：
10.1128/cvi.00299-06
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发表时间：
2007-03-01
影响因子：
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通讯作者：
Adel-Patient, Karine
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文献类型：
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作者：
Cortes-Perez, Naima G.;Ah-Leung, Sandrine;Adel-Patient, Karine
Th 1/Th 2平衡向Th 2免疫应答的失调在变态反应中起核心作用。我们以前证明，管理重组乳酸乳球菌菌株表达牛β-乳球蛋白（BLG），一种主要的牛奶过敏原，部分防止小鼠致敏。在本研究中，我们的目的是提高这种预防效果，通过联合使用L。lactis BLG和第二重组L.产生生物活性白细胞介素-12（IL-12）的乳酸菌菌株。这个L。产生IL-12的乳酸菌菌株先前被用于增强肿瘤鼠模型中的Th 1免疫应答（L. G. Escherich-Humaran等人，175：7297-7302，2005）。对单独施用BLG或在IL-12存在下施用BLG进行比较。BLG特异性的初级Th 1免疫应答仅在鼻内联合施用两种L. lactis BLG和IL-12产生菌L.乳酸杆菌，如通过诱导血清特异性免疫球蛋白G2 a（IgG 2a）伴随脾细胞分泌γ干扰素所证明的，证实了产生IL-12的L.乳。免疫小鼠腹腔注射纯化的BLG进一步致敏，并用纯化的BLG鼻内激发引起过敏反应。在存在或不存在IL-12的情况下用BLG预处理的小鼠对进一步的过敏性致敏和诱发完全耐受。用L. lactis BLG或L. lactis BLG和IL-12产生菌L.乳酸菌诱导血清和支气管肺泡灌洗液（BAL）中产生特异性抗BLG IgG 2a。虽然这些预处理对血清特异性IgE没有影响，但在BLG激发后，L预处理组的BALF中嗜酸性粒细胞和IL-5分泌水平显著降低。lactis BLG和L.乳酸菌BLG-IL-12产生菌乳酸，表明过敏反应降低。我们的数据首次证明了（i）通过L. lactis BLG和IL-12产生菌L.乳酸菌，其抑制小鼠对BLG的过敏反应的诱发和（ii）BLG的鼻内给药诱导耐受性的效率。
The Th1/Th2 balance deregulation toward a Th2 immune response plays a central role in allergy. We previously demonstrated that administration of recombinant Lactococcus lactis strains expressing bovine P-lactoglobulin (BLG), a major cow's milk allergen, partially prevents mice from sensitization. In the present study, we aimed to improve this preventive effect by coadministration of L. lactis BLG and a second recombinant L. lactis strain producing biologically active interieukin-12 (IL-12). This L. lactis strain producing IL-12 was previously used to enhance the Th1 immune response in a tumoral murine model (L. G. Bermudez-Humaran et al., J. Immunol. 175:7297-7302, 2005). A comparison of the administration of either BLG alone or BLG in the presence of IL-12 was conducted. A BLG-specific primary Th1 immune response was observed only after intranasal coadministration of both L. lactis BLG and IL-12-producing L. lactis, as demonstrated by the induction of serum-specific immunoglobulin G2a (IgG2a) concomitant with gamma interferon secretion by splenocytes, confirming the adjuvanticity of IL-12-producing L. lactis. Immunized mice were further sensitized by intraperitoneal administration of purified BLG, and the allergic reaction was elicited by intranasal challenge with purified BLG. Mice pretreated with BLG in either the presence or the absence of IL-12 were rendered completely tolerant to further allergic sensitization and elicitation. Pretreatment with either L. lactis BLG or L. lactis BLG and IL-12-producing L. lactis induces specific anti-BLG IgG2a production in serum and bronchoalveolar lavage (BAL) fluid. Although specific serum IgE was not affected by these pretreatments, the levels of eosinophilia and IL-5 secretion in BAL fluid were significantly reduced after BLG challenge in the groups pretreated with L. lactis BLG and L. lactis BLG-IL-12-producing L. lactis, demonstrating a decreased allergic reaction. Our data demonstrate for the first time (i) the induction of a protective Th1 response by the association of L. lactis BLG and IL-12-producing L. lactis which inhibits the elicitation of the allergic reaction to BLG in mice and (ii) the efficiency of intranasal administration of BLG for the induction of tolerance.