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Protection against allergic airway inflammation during the chronic and acute phases of Trichinella spiralis infection

机译：在旋毛虫感染的慢性和急性阶段预防变应性气道炎症

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Background: Modulation of the host immune response by helminths has been reported to be essential for parasite survival and also to benefit the host by suppressing inflammatory diseases such as allergies. We have previously shown that excretory-secretory products of Trichinella spiralis muscle larvae have immunomodulatory properties and induce in vitro the expansion of CD4+CD25+FOXP3+ Treg cells in a TGF-β-dependent manner. Objective: We aimed at determining the effect of the acute (intestinal) and the chronic (muscle) phase of T. spiralis infection on experimental allergic airway inflammation (EAAI) to Ovalbumin (OVA) and the involvement of Treg cells. Methods: The chronic phase was established before OVA-sensitization/challenge and the acute phase at two-time points, before and after OVA-sensitization. Mice were infected with 400 T. spiralis larvae and after euthanasia different pathological features of EAAI were measured. Adoptive transfer of CD4+ T cells from Trichinella infected mice to OVA sensitized/challenged recipients was also performed. Results: We found that the chronic as well as the acute phase of Trichinella infection suppress EAAI as indicated by reduction in airway inflammation, OVA-specific IgE levels in sera, Th2-cytokine production and eosinophils in bronchoalveolar lavage. This protective effect was found to be stronger during the chronic phase and to be associated with increased numbers of splenic CD4+CD25+FOXP3+ Treg cells with suppressive activity. Adoptive transfer of splenic CD4+ T cells from chronically infected mice with elevated numbers of Treg cells resulted in partial protection against EAAI. Conclusions and Clinical Relevance: These results demonstrate that the protective effect of T. spiralis on EAAI increases as infection progresses from the acute to the chronic phase. Here, Treg cells may play an essential role in the suppression of EAAI. Elucidating the mechanisms and molecular helminth structures responsible for this regulatory process is relevant to develop alternative tools for preventing or treating allergic asthma.
机译：背景：据报道，蠕虫对宿主免疫反应的调节对于寄生虫的生存至关重要，并且还可以通过抑制发炎性疾病（例如过敏症）使宿主受益。先前我们已经证明旋毛虫旋毛虫肌幼虫的排泄分泌产物具有免疫调节特性，并以TGF-β依赖性方式体外诱导CD4 + CD25 + FOXP3 + Treg细胞的扩增。目的：我们旨在确定螺旋螺旋体感染的急性（肠）和慢性（肌肉）期对卵清蛋白（OVA）的实验性过敏性气道炎症（EAAI）和Treg细胞的侵袭的影响。方法：在OVA敏化/挑战之前建立慢性期，在OVA敏化之前和之后的两个时间点建立急性期。将小鼠感染400个螺旋螺旋体幼虫，并在安乐死后测量EAAI的不同病理特征。还进行了将Trichinella感染小鼠的CD4 + T细胞过继转移至OVA致敏/激发的接受者。结果：我们发现，旋毛虫感染的慢性和急性期均抑制了EAAI，如气道炎症，血清中OVA特异性IgE水平降低，Th2细胞因子生成和支气管肺泡灌洗中嗜酸性粒细胞减少所表明。发现这种保护作用在慢性期更强，并且与具有抑制活性的脾脏CD4 + CD25 + FOXP3 + Treg细胞数量增加有关。从Treg细胞数量增加的慢性感染小鼠中脾脏CD4 + T细胞的过继转移导致对EAAI的部分保护。结论和临床意义：这些结果表明，螺旋杆菌对EAAI的保护作用随着感染从急性期向慢性期的发展而增加。在这里，Treg细胞可能在抑制EAAI中起重要作用。阐明负责此调节过程的机制和分子蠕虫结构与开发预防或治疗过敏性哮喘的替代工具有关。

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