Enhancement of Th1 Lung Immunity Induced by Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Attenuates Airway Allergic Disease
Enhancement of Th1 Lung Immunity Induced by Recombinant Mycobacterium bovis Bacillus Calmette-Guerin Attenuates Airway Allergic Disease
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DOI：
10.1165/rcmb.2009-0040oc
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发表时间：
2010-08-01
影响因子：
6.4
通讯作者：
Russo, Momtchilo
中科院分区：
文献类型：
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作者：
Christ, Ana P.;Rodriguez, Dunia;Russo, Momtchilo
牛分枝杆菌卡介苗（BCG）已被证明可以下调实验性过敏性哮喘，这一发现加强了卫生假说。我们之前发现表达百日咳毒素遗传解毒Si亚基（rBCG- s1pt）的重组卡介苗（rBCG）菌株发挥佐剂作用，增强Th1对卡介苗蛋白的应答。在此，我们研究了rBCG-S1PT对经典卵清蛋白诱导的小鼠变应性肺病模型的影响。我们发现rBCG-S1PT在预防th2介导的过敏免疫反应方面比野生型卡介苗更有效。过敏性肺病的抑制与抑制性细胞因子浓度的增加或肺调节性T细胞数量的增加无关，但与肺中产生ifn - γ的T细胞和T-bet表达的增加呈正相关。此外，il -12依赖性机制似乎对肺变应性疾病的抑制很重要。发现对变应性炎症的抑制仅限于肺部，因为当通过腹腔途径给药时，rBCG-S1PT不能抑制腹膜变应性炎症和2型细胞因子的产生。我们的工作为卫生假说提供了一种非经典的解释，表明rBCG对肺部过敏的减弱可能是由于rBCG- s1pt诱导的局部肺Th1免疫的增强。此外，它强调了rBCG菌株作为多用途免疫调节剂的可能性，通过诱导对微生物产物的特异性免疫，同时保护过敏性哮喘。
Mycobacterium bovis Bacillus Calmette-Guerin (BCG) has been shown to down-regulate experimental allergic asthma, a finding that reinforced the hygiene hypothesis. We have previously found that recombinant BCG (rBCG) strain that express the genetically detoxified Si subunit of pertussis toxin (rBCG-S1PT) exerts an adjuvant effect that enhances Th1 responses against BCG proteins. Here we investigated the effect of this rBCG-S1PT on the classical ovalbumin-induced mouse model of allergic lung disease. We found that rBCG-S1PT was more effective than wild-type BCG in preventing Th2-mediated allergic immune responses. The inhibition of allergic lung disease was not associated with increased concentration of suppressive cytokines or with an increased number of pulmonary regulatory T cells but was positively correlated with the increase in IFN-gamma-producing T cells and T-bet expression in the lung. In addition, an IL-12-dependent mechanism appeared to be important to the inhibition of lung allergic disease. The inhibition of allergic inflammation was found to be restricted to the lung because when allergen challenge was given by the intraperitoneal route, rBCG-S1PT administration failed to inhibit peritoneal allergic inflammation and type 2 cytokine production. Our work offers a nonclassical interpretation for the hygiene hypothesis indicating that attenuation of lung allergy by rBCG could be due to the enhancement of local lung Th1 immunity induced by rBCG-S1PT. Moreover, it highlights the possible use of rBCG strains as multipurpose immunomodulators by inducing specific immunity against microbial products while protecting against allergic asthma.