Human Gut Commensal Membrane Vesicles Modulate Inflammation by Generating M2-like Macrophages and Myeloid-Derived Suppressor Cells
Human Gut Commensal Membrane Vesicles Modulate Inflammation by Generating M2-like Macrophages and Myeloid-Derived Suppressor Cells
复制标题
人肠道共生膜囊泡通过产生M2样巨噬细胞和髓源性抑制细胞调节炎症
DOI：
10.4049/jimmunol.2000731
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发表时间：
2020-11-15
影响因子：
4.4
通讯作者：
Gursel, Mayda
中科院分区：
文献类型：
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作者：
Bulut, Esin Alpdundar;Kocabas, Banu Bayyurt;Gursel, Mayda
免疫调节共生细菌通过将调节性微生物衍生产物递送至宿主细胞来改变宿主免疫力。共生体分泌的细胞外膜囊泡（MV）代表了一种这样的运输机制。 MV 如何发挥其抗炎作用或它们的耐受诱导潜力是否可用于治疗目的仍不清楚。在这项研究中，我们发现从人乳酸共生菌戊糖片球菌中分离出的MV可抑制Ag特异性体液和细胞反应。 MV 治疗骨髓源性巨噬细胞和骨髓祖细胞分别促进 M2 样巨噬细胞极化和骨髓源性抑制细胞分化，最有可能以 TLR2 依赖性方式。与其免疫调节活性一致，MV 分化细胞上调 IL-10、精氨酸酶-1 和 PD-L1 的表达，并抑制活化 T 细胞的增殖。 MV 的抗炎作用在小鼠急性炎症模型中得到了进一步测试。在四氯化碳诱导的纤维化和酵母聚糖诱导的腹膜炎模型中，MV 可改善炎症。在右旋糖酐硫酸钠诱导的急性结肠炎模型中，MVs 全身治疗可防止结肠缩短和隐窝结构丧失。在切除伤口愈合模型中，腹腔注射。 MV 给药通过将表达 PD-L1 的骨髓细胞募集到伤口部位来加速伤口闭合。总的来说，这些结果表明戊糖丙酸杆菌衍生的 MV 有希望作为治疗剂来控制/治疗炎症状况。
Immunomodulatory commensal bacteria modify host immunity through delivery of regulatory microbial-derived products to host cells. Extracellular membrane vesicles (MVs) secreted from symbiont commensals represent one such transport mechanism. How MVs exert their anti-inflammatory effects or whether their tolerance-inducing potential can be used for therapeutic purposes remains poorly defined. In this study, we show that MVs isolated from the human lactic acid commensal bacteria Pediococcus pentosaceus suppressed Ag-specific humoral and cellular responses. MV treatment of bone marrow-derived macrophages and bone marrow progenitors promoted M2-like macrophage polarization and myeloid-derived suppressor cell differentiation, respectively, most likely in a TLR2-dependent manner. Consistent with their immunomodulatory activity, MV-differentiated cells upregulated expression of IL-10, arginase-1, and PD-L1 and suppressed the proliferation of activated T cells. MVs' antiinflammatory effects were further tested in acute inflammation models in mice. In carbon tetrachloride-induced fibrosis and zymosan-induced peritonitis models, MVs ameliorated inflammation. In the dextran sodium sulfate-induced acute colitis model, systemic treatment with MVs prevented colon shortening and loss of crypt architecture. In an excisional wound healing model, i.p. MV administration accelerated wound closure through recruitment of PD-L1-expressing myeloid cells to the wound site. Collectively, these results indicate that P pentosaceus-derived MVs hold promise as therapeutic agents in management/treatment of inflammatory conditions.