柠檬酸杆菌
微生物学
生物
白细胞介素22
肠道菌群
抗菌剂
柠檬酸杆菌
免疫学
肠杆菌科
白细胞介素
病菌
细胞因子
大肠杆菌
基因
生物化学
作者
José Luís Fachi,Blanda Di Luccia,Susan Gilfillan,Hyuksang Chang,Christina Song,Jiye Cheng,Marina Cella,Marco Aurélio Ramirez Vinolo,Jeffrey I. Gordon,Marco Colonna
标识
DOI:10.1073/pnas.2321836121
摘要
Interleukin 22 (IL-22) promotes intestinal barrier integrity, stimulating epithelial cells to enact defense mechanisms against enteric infections, including the production of antimicrobial peptides. IL-22 binding protein (IL-22BP) is a soluble decoy encoded by the Il22ra2 gene that decreases IL-22 bioavailability, attenuating IL-22 signaling. The impact of IL-22BP on gut microbiota composition and functioning is poorly understood. We found that Il22ra2 –/– mice are better protected against Clostridioides difficile and Citrobacter rodentium infections. This protection relied on IL-22-induced antimicrobial mechanisms before the infection occurred, rather than during the infection itself. Indeed, the gut microbiota of Il22ra2 –/– mice mitigated infection of wild-type (WT) mice when transferred via cohousing or by cecal microbiota transplantation. Indicator species analysis of WT and Il22ra2 –/– mice with and without cohousing disclosed that IL22BP deficiency yields a gut bacterial composition distinct from that of WT mice. Manipulation of dietary fiber content, measurements of intestinal short-chain fatty acids and oral treatment with acetate disclosed that resistance to C. difficile infection is related to increased production of acetate by Il22ra2 –/– -associated microbiota. Together, these findings suggest that IL-22BP represents a potential therapeutic target for those at risk for or with already manifest infection with this and perhaps other enteropathogens.
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