Kearney Sean Christopher, Dziekiewicz Marcin, Feleszko Wojciech
Department of Pediatric Respiratory and Allergic Diseases, Medical University of Warsaw, Warsaw, Poland.
Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, Warsaw, Poland.
Ann Allergy Asthma Immunol. 2015 May;114(5):364-9. doi: 10.1016/j.anai.2015.02.008. Epub 2015 Mar 6.
This review focuses on the current understanding of the molecular mechanisms of bacterial lysates, evidence of an induction of innate immunity, and the interaction with immunoregulators, dendritic cells, and regulatory T cells. Clinical relevance is summarized based on the observed mechanisms of action of bacterial lysates.
Academic Search Complete, CENTRAL, Health Source: Nursing/Academic Edition, MEDLINE, and Cochrane databases.
Three independent researchers focused on primary and secondary end points in systematic reviews, meta-analyses, and randomized controlled trials using bacterial lysates as a verum group or within a subpopulation of larger studies. Interventional and observational studies on novel applications also were included. Preclinical studies included murine models focusing on toll-like receptors (TLRs) and regulatory T cells and on the relation with asthma and respiratory immunity.
Bacterial lysates have been observed to induce synergistic TLR-2/6- and TLR-9-dependent innate immunity. It has positive outcomes in decreasing recurrent respiratory tract infections in childhood and adult chronic obstructive pulmonary disease. This class of immunostimulants shows some evidence of mitigating infection morbidity in children and decreasing the frequency of inflammatory episodes (ie, wheezing exacerbations) in children with asthma. Preclinical studies suggest that regulatory T cells can be induced by bacterial lysates and might attenuate T-helper cell type 2 allergic responses.
Although successful prevention against all common respiratory pathogens is not possible, bacterial lysates seem capable of targeting specific immunocompetent cells through pathogen recognition receptor activation. Current challenges include clarifying the duality of immunoregulatory and immunostimulatory responses in children at risk for allergy. Larger clinical trials are required to elicit efficacy in allergy prevention.
本综述聚焦于目前对细菌裂解物分子机制的理解、诱导先天免疫的证据以及与免疫调节因子、树突状细胞和调节性T细胞的相互作用。基于观察到的细菌裂解物作用机制总结其临床相关性。
学术搜索完整版、CENTRAL、健康源：护理/学术版、医学索引数据库和Cochrane数据库。
三位独立研究人员关注系统评价、荟萃分析和随机对照试验中的主要和次要终点，这些试验将细菌裂解物作为试验组或纳入更大规模研究的亚组中。还纳入了关于新应用的干预性和观察性研究。临床前研究包括以Toll样受体（TLR）和调节性T细胞以及与哮喘和呼吸道免疫关系为重点的小鼠模型。
已观察到细菌裂解物可诱导协同的TLR-2/6和TLR-9依赖性先天免疫。它在降低儿童复发性呼吸道感染和成人慢性阻塞性肺疾病方面有积极结果。这类免疫刺激剂显示出一些减轻儿童感染发病率和降低哮喘儿童炎症发作（即喘息加重）频率的证据。临床前研究表明，细菌裂解物可诱导调节性T细胞，并可能减弱2型辅助性T细胞的过敏反应。
尽管不可能成功预防所有常见呼吸道病原体，但细菌裂解物似乎能够通过激活病原体识别受体靶向特定免疫活性细胞。当前的挑战包括阐明过敏风险儿童免疫调节和免疫刺激反应的双重性。需要更大规模的临床试验来确定其在预防过敏方面的疗效。
