肠道菌群组成的变化，即所谓的菌群失调，直接与急性和慢性疾病相关。然而，将肠道菌群失调与全身性炎症病理之间的基础生物系统联系起来尚不完全清楚。磷脂（PLs）既是活性炎症介质的前体，也是解决介质的前体。它们的失调与包括癌症在内的慢性疾病相关联。肠道微生物来源的脂质在结构上独特，并且能够调节宿主的免疫力。约翰逊乳杆菌（Lactobacillus johnsonii）N6.2是一种具有益生特征的革兰氏阳性肠道共生菌。L. johnsonii N6.2通过在1型糖尿病动物模型中减少自身免疫性疾病的发生以及在健康志愿者中通过促进局部和全身抗炎反应来改善整体健康状况。通过利用骨髓源性树突状细胞（BMDCs）的生物鉴定引导的分离方法，我们在此报道了L. johnsonii N6.2纯化脂质诱导的转录特征与迁移（mig）DCs相似。基于RNAseq的分析显示，与L. johnsonii N6.2总脂质刺激的BMDCs诱导成熟迁移相关基因Cd86、Cd40、Ccr7、Icam1以及包括Itgb8、Nfkbiz、Jag1、Adora2a、IL2ra、Arg1和Cd274在内的免疫调控基因上调。定量反转录（qRT）-PCR分析表明PLs是诱导BMDCs反应的活性脂质。表面Toll样受体（TLR）2的抗体阻断增强了PL介导的上调炎性因子Il6。对非典型NF-κB通路中的IKKα激酶进行化学抑制特异性限制了Il6和Tnf的上调。表型上，PL刺激的BMDCs表现出一种幼稚的表型，表面ICAM-1显著增加。本研究揭示了Gram阳性肠道微生物来源的磷脂对先天免疫反应的免疫调节能力。

Shifts in the gut microbiota composition, called dysbiosis, have been directly associated with acute and chronic diseases. However, the underlying biological systems connecting gut dysbiosis to systemic inflammatory pathologies are not well understood. Phospholipids (PLs) act as precursors of both, bioactive inflammatory and resolving mediators. Their dysregulation is associated with chronic diseases including cancer. Gut microbial-derived lipids are structurally unique and capable of modulating host's immunity. Lactobacillus johnsonii N6.2 is a Gram-positive gut symbiont with probiotic characteristics. L. johnsonii N6.2 reduces the incidence of autoimmunity in animal models of Type 1 Diabetes and improves general wellness in healthy volunteers by promoting, in part, local and systemic anti-inflammatory responses. By utilizing bioassay-guided fractionation methods with bone marrow-derived dendritic cells (BMDCs), we report here that L. johnsonii N6.2 purified lipids induce a transcriptional signature that resembles that of migratory (mig) DCs. RNAseq-based analysis showed that BMDCs stimulated with L. johnsonii N6.2 total lipids upregulate maturation-mig related genes Cd86, Cd40, Ccr7, Icam1 along with immunoregulatory genes including Itgb8, Nfkbiz, Jag1, Adora2a, IL2ra, Arg1, and Cd274. Quantitative reverse transcription (qRT)-PCR analysis indicated that PLs are the bioactive lipids triggering the BMDCs response. Antibody-blocking of surface Toll-like receptor (TLR)2 resulted in boosted PL-mediated upregulation of pro-inflammatory Il6. Chemical inhibition of the IKKα kinase from the non-canonical NF-κB pathway specifically restricted upregulation of Il6 and Tnf. Phenotypically, PL-stimulated BMDCs displayed an immature like-phenotype with significantly increased surface ICAM-1. This study provides insight into the immunoregulatory capacity of Gram-positive, gut microbial-derived phospholipids on innate immune responses.