Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen.
Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen.
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DOI：
10.1016/j.chom.2014.08.017
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发表时间：
2014-10-08
影响因子：
30.3
通讯作者：
Lawley TD
中科院分区：
文献类型：
--
作者：
Pham TA;Clare S;Goulding D;Arasteh JM;Stares MD;Browne HP;Keane JA;Page AJ;Kumasaka N;Kane L;Mottram L;Harcourt K;Hale C;Arends MJ;Gaffney DJ;Sanger Mouse Genetics Project;Dougan G;Lawley TD
我们的肠道微生物群拥有多样化的微生物群落，通常含有具有毒力潜力的机会性细菌。然而，互惠宿主-微生物相互作用通过知之甚少的机制预防机会病原体引起的疾病。我们发现，上皮细胞白细胞介素-22受体IL-22 RA 1通过促进对肠道机会性细菌粪肠球菌的定植抵抗来防止致死性啮齿类柠檬酸杆菌感染和化学诱导的结肠炎。Il 22 ra 1 −/−小鼠对啮齿类隐球菌的易感性与严重微生物生态失调期间致病性粪肠球菌的优先扩张和上皮移位有关，并且可以通过对粪肠球菌具有活性的抗生素来改善。原代结肠类器官的RNA测序分析表明，IL-22 RA 1信号转导通过诱导岩藻糖基转移酶Fut 2促进肠道岩藻糖基化。此外，向啮齿类梭菌激发的Il 22 ra 1 −/−小鼠给予岩藻糖基化低聚糖可通过恢复厌氧共生体的多样性来减轻感染并促进粪肠球菌定植抗性。这些结果支持IL-22 RA 1增强宿主-微生物群互惠以限制机会性病原体的有害过度定殖的模型。Il 22 ra 1 −/−小鼠在啮齿类梭菌感染期间死于肠球菌传播粪肠球菌在啮齿类梭菌诱导的生态失调期间扩张并侵入上皮细胞类器官IL-22 RA 1 RNA-seq揭示了多种抗菌和糖基化因子肠道岩藻糖基化增强了对粪肠球菌的定植抗性宿主-宿主相互作用通过知之甚少的机制预防机会性病原体引起的疾病。Pham等人显示IL-22 RA 1信号传导可以通过促进肠岩藻糖基化并因此增强上皮和肠道微生物之间的有益营养相互作用来控制粘膜增殖和随后的机会致病菌的上皮易位。
Our intestinal microbiota harbors a diverse microbial community, often containing opportunistic bacteria with virulence potential. However, mutualistic host-microbial interactions prevent disease by opportunistic pathogens through poorly understood mechanisms. We show that the epithelial interleukin-22 receptor IL-22RA1 protects against lethal Citrobacter rodentium infection and chemical-induced colitis by promoting colonization resistance against an intestinal opportunistic bacterium, Enterococcus faecalis. Susceptibility of Il22ra1−/− mice to C. rodentium was associated with preferential expansion and epithelial translocation of pathogenic E. faecalis during severe microbial dysbiosis and was ameloriated with antibiotics active against E. faecalis. RNA sequencing analyses of primary colonic organoids showed that IL-22RA1 signaling promotes intestinal fucosylation via induction of the fucosyltransferase Fut2. Additionally, administration of fucosylated oligosaccharides to C. rodentium-challenged Il22ra1−/− mice attenuated infection and promoted E. faecalis colonization resistance by restoring the diversity of anaerobic commensal symbionts. These results support a model whereby IL-22RA1 enhances host-microbiota mutualism to limit detrimental overcolonization by opportunistic pathogens. Il22ra1−/− mice succumb to enterococcal dissemination during C. rodentium infection E. faecalis expands during C. rodentium-induced dysbiosis and invades epithelial cells Organoid IL-22RA1 RNA-seq reveals diverse antimicrobial and glycosylation factors Intestinal fucosylation enhances colonization resistance to E. faecalis Host-commensal interactions prevent disease by opportunistic pathogens through poorly understood mechanisms. Pham et al. show that IL-22RA1 signaling can control the mucosal proliferation and subsequent epithelial translocation of an opportunistic pathogen by promoting intestinal fucosylation and thus enhancing beneficial nutrient interactions between the epithelium and commensal microbes.
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影响因子：
30.3
作者：
Martens EC;Chiang HC;Gordon JI
通讯作者：
Gordon JI
影响因子：
30.3
作者：
Marcobal A;Barboza M;Sonnenburg ED;Pudlo N;Martens EC;Desai P;Lebrilla CB;Weimer BC;Mills DA;German JB;Sonnenburg JL
通讯作者：
Sonnenburg JL
影响因子：
12.3
作者：
Bourgogne, Agathe;Garsin, Danielle A.;Qin, Xiang;Singh, Kavindra V.;Sillanpaa, Jouko;Yerrapragada, Shailaja;Ding, Yan;Dugan-Rocha, Shannon;Buhay, Christian;Shen, Hua;Chen, Guan;Williams, Gabrielle;Muzny, Donna;Maadani, Arash;Fox, Kristina A.;Gioia, Jason;Chen, Lei;Shang, Yue;Arias, Cesar A.;Nallapareddy, Sreedhar R.;Zhao, Meng;Prakash, Vittal P.;Chowdhury, Shahreen;Jiang, Huaiyang;Gibbs, Richard A.;Murray, Barbara E.;Highlander, Sarah K.;Weinstock, George M.
通讯作者：
Weinstock, George M.
影响因子：
56.9
作者：
Bry, L;Falk, PG;Gordon, JI
通讯作者：
Gordon, JI
影响因子：
4.9
作者：
HUYCKE, MM;SPIEGEL, CA;GILMORE, MS
通讯作者：
GILMORE, MS