Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.

Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.
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DOI:
10.1038/mi.2017.13
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发表时间:
2017-11
期刊:
影响因子:
8
通讯作者:
Lukacs NW
Lukacs NW
中科院分区:
医学1区
文献类型:
--
作者:
Fonseca W;Lucey K;Jang S;Fujimura KE;Rasky A;Ting HA;Petersen J;Johnson CC;Boushey HA;Zoratti E;Ownby DR;Levine AM;Bobbit KR;Lynch SV;Lukacs NW

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通过微生物衍生的代谢物调节呼吸道粘膜免疫已被提出可能提供气道保护的机制。在这里,我们研究了口服约氏乳杆菌补充剂对呼吸道合胞病毒(RSV)感染期间代谢和免疫反应动力学的影响。L.补充约翰逊氏剂降低了气道Th2细胞因子、树突状细胞功能、增加了T调节细胞,并且与重新编程的循环代谢环境(包括二十二碳六烯酸(DHA)富集)相关。RSV感染L.补充johnsonii的小鼠具有改变的细胞因子分泌、降低的共刺激分子表达和修饰的CD4+ T细胞细胞因子。这在野生型BMDC与来自L.补充约翰逊氏剂的小鼠或DHA。最后,研究了L.补充约氏乳杆菌的小鼠,或用来自约氏乳杆菌的血浆预处理的野生型来源的BMDC。补充johnsonii的小鼠降低了受体动物对感染的气道病理反应。因此,L.约翰逊补充剂通过免疫调节代谢物和改变的免疫功能介导气道粘膜保护。
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 Th2 cytokines, dendritic cell function, increased T-regulatory cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone-marrow derived dendritic cells (BMDC) 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 pre-treated with plasma from L. johnsonii-supplemented mice, reduced airway pathologic responses to infection in recipient animals. Thus, L. johnsonii-supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function.
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