The Liver May Act as a Firewall Mediating Mutualism Between the Host and Its Gut Commensal Microbiota
The Liver May Act as a Firewall Mediating Mutualism Between the Host and Its Gut Commensal Microbiota
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DOI：
10.1126/scitranslmed.3008618
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发表时间：
2014-05-21
影响因子：
17.1
通讯作者：
Macpherson, Andrew J.
中科院分区：
文献类型：
--
作者：
Balmer, Maria L.;Slack, Emma;Macpherson, Andrew J.
宿主和大肠微生物群落之间建立互惠共生的先决条件是微生物的严格粘膜区室化。负载微生物的树突状细胞在肠系膜淋巴结处被阻止，肠系膜淋巴结构成肠淋巴循环的防火墙。我们在不同的小鼠模型中表明，接受肠道静脉血液循环的肝脏形成了一个血管防火墙，在肠道病理过程中捕获进入血液的肠道细菌。小鼠肝脏中的吞噬性库普弗细胞通过肝脏自身的动脉供应独立于脾脏从全身血管系统清除肿瘤。尽管先天免疫增强，但小鼠肝脏防火墙的损伤会损害从血液中清除唾液酸的功能，导致通过增加全身暴露于肠道唾液酸而自发引发非粘膜免疫应答。在肝病（非酒精性脂肪性肝炎）患者中发现了与肠外肠道暴露增加一致的全身免疫反应。肝脏可以作为功能性血管防火墙，清除穿透肠或全身血管回路的血管。
A prerequisite for establishment of mutualism between the host and the microbial community that inhabits the large intestine is the stringent mucosal compartmentalization of microorganisms. Microbe-loaded dendritic cells trafficking through lymphatics are arrested at the mesenteric lymph nodes, which constitute the firewall of the intestinal lymphatic circulation. We show in different mouse models that the liver, which receives the intestinal venous blood circulation, forms a vascular firewall that captures gut commensal bacteria entering the bloodstream during intestinal pathology. Phagocytic Kupffer cells in the liver of mice clear commensals from the systemic vasculature independently of the spleen through the liver's own arterial supply. Damage to the liver firewall inmice impairs functional clearance of commensals from blood, despite heightened innate immunity, resulting in spontaneous priming of nonmucosal immune responses through increased systemic exposure to gut commensals. Systemic immune responses consistent with increased extraintestinal commensal exposure were found in humans with liver disease (nonalcoholic steatohepatitis). The liver may act as a functional vascular firewall that clears commensals that have penetrated either intestinal or systemic vascular circuits.