Epithelial IL-22RA1-Mediated Fucosylation Promotes Intestinal Colonization Resistance to an Opportunistic Pathogen

被引：272

作者：

Pham, Tu Anh N. ^{[1
]}

Clare, Simon ^{[1
]}

Goulding, David ^{[1
]}

Arasteh, Julia M. ^{[1
]}

Stares, Mark D. ^{[1
]}

Browne, Hilary P. ^{[1
]}

Keane, Jacqueline A. ^{[1
]}

Page, Andrew J. ^{[1
]}

Kumasaka, Natsuhiko ^{[1
]}

Kane, Leanne ^{[1
]}

Mottram, Lynda ^{[1
]}

Harcourt, Katherine ^{[1
]}

Hale, Christine ^{[1
]}

Arends, Mark J. ^{[2
]}

Gaffney, Daniel J. ^{[1
]}

Dougan, Gordon ^{[1
]}

Lawley, Trevor D. ^{[1
]}

机构：

[1] Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England

[2] Univ Cambridge, Addenbrookes Hosp, Dept Pathol, Cambridge CB2 0QQ, England

来源：

CELL HOST & MICROBE | 2014年 / 16卷 / 04期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

ENTEROCOCCUS-FAECALIS; HOST-DEFENSE; GENOME-WIDE; MICROBIOTA; IL-22; GUT; INFECTION; IMMUNITY; BACTERIA; DISEASE;

D O I：

10.1016/j.chom.2014.08.017

中图分类号：

Q93 [微生物学];

学科分类号：

071005 [微生物学];

摘要：

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.

引用

页码：504 / 516

页数：13

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