Gut microbiome communication with bone marrow regulates susceptibility to amebiasis

Gut microbiome communication with bone marrow regulates susceptibility to amebiasis
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DOI:
10.1101/487652
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发表时间:
2018-12
期刊:
The Journal of Clinical Investigation
影响因子:
--
通讯作者:
S. Burgess;J. Leslie;Md Jashim Uddin;Noah Oakland;Koji Watanabe;C. Gilchrist;Mahmoud M. Saleh;M. Simpson;S. Turner;Natasa Giallourou;J. Swann;R. Haque;W. Petri
S. Burgess;J. Leslie;Md Jashim Uddin;Noah Oakland;Koji Watanabe;C. Gilchrist;Mahmoud M. Saleh;M. Simpson;S. Turner;Natasa Giallourou;J. Swann;R. Haque;W. Petri
中科院分区:
其他
文献类型:
--
作者:
S. Burgess;J. Leslie;Md Jashim Uddin;Noah Oakland;Koji Watanabe;C. Gilchrist;Mahmoud M. Saleh;M. Simpson;S. Turner;Natasa Giallourou;J. Swann;R. Haque;W. Petri

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肠道微生物群可能提供对感染的抵抗力。然而,人们对其机制知之甚少。我们发现,肠道细菌梭状芽胞杆菌对溶组织内阿米巴寄生虫具有免疫力。将C. scindens定植小鼠的骨髓过继移植到naïve-mice可预防阿米巴结肠炎并增加肠道中性粒细胞。引入scindens可引起骨髓粒细胞-单核细胞-祖细胞(GMPs)的扩增,并增加GMPs中表观遗传介质JMJD3的表达。去氧胆酸盐在C. scindens定植小鼠的血清中增加,以及在受阿米巴病保护的儿童中。单独给药脱氧胆酸盐(在没有C. scindens的情况下)增加了JMJD3和gmp,并提供了对阿米巴病的保护。这项工作证明了微生物组与骨髓的交流导致先天免疫记忆和抗原非特异性保护阿米巴病。
The gut microbiome may provide resistance to infection. However, the mechanisms for this are poorly understood. We found that the intestinal bacterium Clostridium scindens provided immunity to the parasite Entamoeba histolytica. Adoptive transfer of bone-marrow from C. scindens colonized-mice into naïve-mice protected against amebic colitis and increased intestinal neutrophils. Introduction of C. scindens caused expansion of marrow granulocyte-monocyte-progenitors (GMPs) and increased expression of the epigenetic mediator JMJD3 in GMPs. Deoxycholate was increased in the sera of C. scindens colonized mice, as well as in children protected from amebiasis. Administration of deoxycholate alone (in the absence of C. scindens) increased JMJD3 and GMPs and provided protection from amebiasis. This work demonstrates microbiome to bone marrow communication resulting in innate immune memory and antigen-nonspecific protection from amebiasis.