Critical Role for a Subset of Intestinal Macrophages in Shaping Gut Microbiota in Adult Zebrafish.
Critical Role for a Subset of Intestinal Macrophages in Shaping Gut Microbiota in Adult Zebrafish.
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DOI：
10.1016/j.celrep.2018.09.025
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发表时间：
2018-10-09
期刊：
影响因子：
8.8
通讯作者：
Shiau CE
中科院分区：
文献类型：
--
作者：
Earley AM;Graves CL;Shiau CE
肠道微生物群受到环境因素的强烈影响，尽管宿主的贡献远未被理解。我们利用巨噬细胞缺陷型干扰素调节因子irf8斑马鱼突变体来研究巨噬细胞在这一过程中的作用。在常规饲养的成年irf8缺陷突变体中，我们发现与共同饲养的兄弟姐妹相比，肠道巨噬细胞的显著损失与肠道微生物群的显著改变有关。肠道肠道微生物群的不稳定与补体C1q基因的严重减少和罕见细菌物种的生长有关。与irf8在成年肠道巨噬细胞中的关键功能一致，irf8在这些细胞中正常地大量表达，并且在irf8突变体中恢复巨噬细胞irf8表达足以恢复肠道微生物和C1q基因表达。这项研究报告了一个重要的肠道巨噬细胞亚群，它需要irf8在肠道中建立，确保肠道微生物的正常定植，并防止免疫失调。肠道巨噬细胞是否形成成人肠道微生物群尚未得到证实。Shiau等人表明，成年斑马鱼irf8突变体中肠道巨噬细胞的严重损失可导致肠道微生物群的不稳定和C1q表达的减少。巨噬细胞特异性拯救irf8突变体可以逆转这些影响。
The gut microbiota is strongly influenced by environmental factors, although host contribution is far less understood. We leveraged macrophage-deficient interferon regulatory factor irf8 zebrafish mutants to investigate the role of macrophages in this process. In conventionally raised adult irf8-deficient mutants, we found a significant loss of intestinal macrophages associated with a strikingly altered gut microbiota when compared to co-housed siblings. The destabilization of the gut commensal microbiota was associated with a severe reduction in complement C1q genes and outgrowth of a rare bacterial species. Consistent with a critical function of irf8 in adult intestinal macrophages, irf8 is abundantly expressed in these cells normally, and restoring macrophage irf8 expression in irf8 mutants was sufficient to recover commensal microbes and C1q genes expression. This study reports an important subpopulation of intestinal macrophages that requires irf8 to establish in the gut, ensure normal colonization of gut microbes, and prevent immune dysregulation. Whether intestinal macrophages shape adult gut microbiota has not been demonstrated. Shiau et al. show that a severe loss of intestinal macrophages in adult zebrafish irf8 mutants can cause destabilization of gut commensal microbiota and a reduction of C1q expressions. Macrophage-specific rescue of irf8 mutants can reverse these effects.
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DOI：
10.1016/j.bbrc.2013.08.017
发表时间：
2013-09-13
影响因子：
3.1
作者：
Eom, Ji;Hong, Minsun;Song, Youngsup
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
SCHILLING, TF
影响因子：
3.5
作者：
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通讯作者：
de Vos, Willem M.
影响因子：
29.4
作者：
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通讯作者：
Nieuwenhuis, Edward E. S.