Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis.
Bone marrow dendritic cells from mice with an altered microbiota provide interleukin 17A-dependent protection against Entamoeba histolytica colitis.
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DOI：
10.1128/mbio.01817-14
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发表时间：
2014-11-04
期刊：
影响因子：
6.4
通讯作者：
Petri WA Jr
中科院分区：
文献类型：
--
作者：
Burgess SL;Buonomo E;Carey M;Cowardin C;Naylor C;Noor Z;Wills-Karp M;Petri WA Jr
有一种新的范式，即人类微生物组是健康的许多方面的核心，并可能在预防肠道感染中发挥作用。溶组织内阿米巴是发展中国家阿米巴腹泻的主要原因。它在靠近肠道微生物群的结肠腔中定殖。有趣的是，并非所有个体都同样易受溶组织肠球菌感染。因此，由于微生物群在个体内高度可变，我们试图确定微生物群的一个组成部分是否可以调节对感染的易感性。在利用小鼠模型的研究中，我们证明了肠道中具有肠道梭菌相关细菌（称为分节丝状细菌（SFB））的定殖在溶组织肠球菌感染期间具有保护作用。该模型中SFB定植与盲肠白细胞介素17 A（IL-17 A）、树突状细胞和中性粒细胞水平升高相关。来自SFB定植小鼠的骨髓来源的树突状细胞（BMDCs）在滋养体刺激下产生更高水平的IL-23。将BMDC从SFB+小鼠连续转移至SFB−小鼠足以提供针对溶组织艾美耳球虫的保护。在BMDC转移过程中诱导IL-17 A对于这种保护是必要的。这项工作表明，肠道定植与特定的肠道细菌可以提供保护，在阿米巴病在小鼠模型。最重要的是，这项工作表明，微生物组可以通过对骨髓来源的树突状细胞的肠外作用介导对肠道感染的保护。溶组织内阿米巴是阿米巴病的病原体，阿米巴病是一种传染病，在发展中国家由于腹泻而导致发病率和死亡率显著增加。我们在小鼠模型中表明，梭菌的肠道成员（称为SFB）的定殖提供了针对溶组织肠球菌的保护，并且来自SFB定殖小鼠的树突状细胞单独可以重现保护作用。了解肠道病原体、肠道细菌和粘膜免疫反应（包括树突状细胞）之间的相互作用，将有助于开发针对这种疾病和其他感染性和炎症性疾病的有效治疗方法。由于从微生物组到骨髓的通信，免疫介导的保护的证明代表了一个新兴的研究领域，将为这些治疗的开发提供独特的方法。
There is an emerging paradigm that the human microbiome is central to many aspects of health and may have a role in preventing enteric infection. Entamoeba histolytica is a major cause of amebic diarrhea in developing countries. It colonizes the colon lumen in close proximity to the gut microbiota. Interestingly, not all individuals are equally susceptible to E. histolytica infection. Therefore, as the microbiota is highly variable within individuals, we sought to determine if a component of the microbiota could regulate susceptibility to infection. In studies utilizing a murine model, we demonstrated that colonization of the gut with the commensal Clostridia-related bacteria known as segmented filamentous bacteria (SFB) is protective during E. histolytica infection. SFB colonization in this model was associated with elevated cecal levels of interleukin 17A (IL-17A), dendritic cells, and neutrophils. Bone marrow-derived dendritic cells (BMDCs) from SFB-colonized mice had higher levels of IL-23 production in response to stimulation with trophozoites. Adoptive transfer of BMDCs from an SFB+ to an SFB− mouse was sufficient to provide protection against E. histolytica. IL-17A induction during BMDC transfer was necessary for this protection. This work demonstrates that intestinal colonization with a specific commensal bacterium can provide protection during amebiasis in a murine model. Most importantly, this work demonstrates that the microbiome can mediate protection against an enteric infection via extraintestinal effects on bone marrow-derived dendritic cells. Entamoeba histolytica is the causative agent of amebiasis, an infectious disease that contributes significantly to morbidity and mortality due to diarrhea in the developing world. We showed in a murine model that colonization with the commensal members of the Clostridia known as SFB provides protection against E. histolytica and that dendritic cells from SFB-colonized mice alone can recapitulate protection. Understanding interactions between enteropathogens, commensal intestinal bacteria, and the mucosal immune response, including dendritic cells, will help in the development of effective treatments for this disease and other infectious and inflammatory diseases. The demonstration of immune-mediated protection due to communication from the microbiome to the bone marrow represents an emerging field of study that will yield unique approaches to the development of these treatments.