Role of Serum Amyloid A, Granulocyte-Macrophage Colony-Stimulating Factor, and Bone Marrow Granulocyte-Monocyte Precursor Expansion in Segmented Filamentous Bacterium-Mediated Protection from Entamoeba histolytica
Role of Serum Amyloid A, Granulocyte-Macrophage Colony-Stimulating Factor, and Bone Marrow Granulocyte-Monocyte Precursor Expansion in Segmented Filamentous Bacterium-Mediated Protection from Entamoeba histolytica
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DOI：
10.1128/iai.00316-16
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发表时间：
2016-10-01
影响因子：
3.1
通讯作者：
Petri, William A., Jr.
中科院分区：
文献类型：
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作者：
Burgess, Stacey L.;Saleh, Mahmoud;Petri, William A., Jr.
肠分节丝状菌（SFB）保护免受阿米巴感染，保护作用可通过骨髓树突状细胞（BMDC）转移。SFB引起血清淀粉样蛋白A（SAA）升高，提示SAA可能介导了SFB对BMDCs的作用。在此，我们进一步探讨了骨髓在SFB介导的保护中的作用。短暂的肠道定植与SFB或SAA管理单独短暂增加H3 K27组蛋白去甲基化酶Jmjd 3，持续增加骨髓Csf 2 ra表达和粒细胞单核细胞前体（GMP），并保护阿米巴感染。SAA处理期间Jmjd 3 H3 K27脱甲基酶活性的药理学抑制或SFB定殖小鼠中粒细胞-巨噬细胞集落刺激因子（GM-CSF）信号传导的阻断阻止GMP扩增，减少肠道嗜中性粒细胞，并阻断对阿米巴感染的保护。这些结果表明，微生物群的改变和全身暴露于SAA可以通过表观遗传机制影响骨髓生成和对阿米巴病的易感性。肠道微生物群-骨髓通讯是一种以前未被认识到的先天保护机制。
Intestinal segmented filamentous bacteria (SFB) protect from ameba infection, and protection is transferable with bone marrow dendritic cells (BMDCs). SFB cause an increase in serum amyloid A (SAA), suggesting that SAA might mediate SFB's effects on BMDCs. Here we further explored the role of bone marrow in SFB-mediated protection. Transient gut colonization with SFB or SAA administration alone transiently increased the H3K27 histone demethylase Jmjd3, persistently increased bone marrow Csf2ra expression and granulocyte monocyte precursors (GMPs), and protected from ameba infection. Pharmacologic inhibition of Jmjd3 H3K27 demethylase activity during SAA treatment or blockade of granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling in SFB-colonized mice prevented GMP expansion, decreased gut neutrophils, and blocked protection from ameba infection. These results indicate that alteration of the microbiota and systemic exposure to SAA can influence myelopoiesis and susceptibility to amebiasis via epigenetic mechanisms. Gut microbiota-marrow communication is a previously unrecognized mechanism of innate protection from infection.