Forsythe Paul
1 Firestone Institute for Respiratory Health and Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
Ann Am Thorac Soc. 2014 Jan;11 Suppl 1:S33-7. doi: 10.1513/AnnalsATS.201306-156MG.
There is increasing interest in the potential for microbe-based therapeutic approaches to asthma and respiratory infection. However, to date, clinical trials of probiotics in the treatment of respiratory disease have met with limited success. It is becoming clear that to identify the true therapeutic potential of microbes we must move away from a purely empirical approach to clinical trials and adopt knowledge-based selection of candidate probiotics strains, dose, and means of administration. Animal models have played a key role in the identification of mechanisms underlying the immunomodulatory capacity of specific bacteria. Microbe-induced changes in dendritic cell phenotype and function appear key to orchestrating the multiple pathways, involving inter alia, T cells, natural killer cells, and alveolar macrophages, associated with the protective effect of probiotics. Moving forward, the development of knowledge-based strategies for microbe-based therapeutics in respiratory disease will be aided by greater understanding of how specific bacterial structural motifs activate unique combinations of pattern recognition receptors on dendritic cells and thus direct desired immune responses.
基于微生物的治疗方法在哮喘和呼吸道感染方面的潜力正受到越来越多的关注。然而，迄今为止，益生菌治疗呼吸道疾病的临床试验取得的成功有限。越来越明显的是，为了确定微生物真正的治疗潜力，我们必须摒弃纯粹基于经验的临床试验方法，采用基于知识的方法来选择候选益生菌菌株、剂量和给药方式。动物模型在确定特定细菌免疫调节能力的潜在机制方面发挥了关键作用。微生物诱导的树突状细胞表型和功能变化似乎是协调多种途径的关键，这些途径尤其涉及与益生菌保护作用相关的T细胞、自然杀伤细胞和肺泡巨噬细胞。展望未来，对特定细菌结构基序如何激活树突状细胞上模式识别受体的独特组合从而引导所需免疫反应的更深入理解，将有助于开发基于知识的呼吸道疾病微生物治疗策略。
