Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Department of Medicine, University of California San Francisco, San Francisco, California, USA.
Mucosal Immunol. 2017 Nov;10(6):1569-1580. doi: 10.1038/mi.2017.13. Epub 2017 Mar 15.
Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone marrow-derived DCs (BMDCs) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T-cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice or with wild-type derived BMDCs pretreated with plasma from L. johnsonii-supplemented mice reduced airway pathological responses to infection in recipient animals. Thus L. johnsonii supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function.
微生物衍生代谢物对呼吸黏膜免疫的调节作用是一种可能提供气道保护的机制。在这里，我们研究了口服补充约翰逊乳杆菌对呼吸道合胞病毒 (RSV) 感染期间代谢和免疫反应动态的影响。约翰逊乳杆菌补充剂减少了气道辅助性 T 细胞 2 型细胞因子和树突状细胞 (DC) 的功能，增加了调节性 T 细胞，并与循环代谢环境的重新编程有关，包括二十二碳六烯酸 (DHA) 的富集。来自补充了约翰逊乳杆菌的小鼠的 RSV 感染的骨髓来源的 DC（BMDC）具有改变的细胞因子分泌、共刺激分子表达减少以及修饰的 CD4+T 细胞细胞因子。当与来自补充了约翰逊乳杆菌的小鼠的血浆或 DHA 共孵育时，也复制了这种情况。最后，来自补充了约翰逊乳杆菌的小鼠的 BMDC 或用来自补充了约翰逊乳杆菌的小鼠的血浆预处理的源自野生型的 BMDC 的气道转移减少了受体动物对感染的气道病理反应。因此，约翰逊乳杆菌补充剂通过免疫调节代谢物和改变的免疫功能介导气道黏膜保护。
