دورية أكاديمية
Two ST11 Klebsiella pneumoniae strains exacerbate colorectal tumorigenesis in a colitis-associated mouse model
العنوان: | Two ST11 Klebsiella pneumoniae strains exacerbate colorectal tumorigenesis in a colitis-associated mouse model |
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المؤلفون: | Ming-Ko Chiang, Pei-Yi Hsiao, Yen-Yi Liu, Hui-Ling Tang, Chien-Shun Chiou, Min-Chi Lu, Yi-Chyi Lai |
المصدر: | Gut Microbes, Vol 13, Iss 1 (2021) |
بيانات النشر: | Taylor & Francis Group, 2021. |
سنة النشر: | 2021 |
المجموعة: | LCC:Diseases of the digestive system. Gastroenterology |
مصطلحات موضوعية: | klebsiella pneumoniae, st11, colorectal tumorigenesis, il-10, m2 macrophages, Diseases of the digestive system. Gastroenterology, RC799-869 |
الوصف: | Sequence type (ST) 11 is one of the major lineages of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although the gastrointestinal (GI) carriage of CRKP predisposes individuals to subsequent infections, little is known for its impact on gut homeostasis. In this study, we investigated the association between ST11 CRKP colonization and colorectal cancer (CRC). Two ST11 CRKP, KPC160111 (KL47) and KPC160132 (KL64), were selected as the representative strains. We used azoxymethane (AOM) and dextran sodium sulfate (DSS) to initiate a colitis-associated CRC model. Both strains established prolonged colonization in the GI tract of the AOM-DSS-treated BALB/c mice and aggravated gut dysbiosis. Under this AOM-DSS-induced setting, ST11 K. pneumoniae colonization significantly promoted the growth and progression of colorectal adenomas to high-grade dysplasia. Numerous crypts were formed inside the enlarged adenomas, in which CD163+ tumor-associated macrophages accumulated. Similarly, ST11 K. pneumoniae also increased the population size of the CD163+ macrophages with the M2 phenotype in the peritoneal cavity of LPS-primed BALB/c mice. When applied to RAW264.7 cells, ST11 K. pneumoniae polarized the macrophages toward an M2 phenotype through the inhibition of IKK-NFκB and the activation of STAT6-KLF4-IL-10. Through the M2-skewing ability, ST11 K. pneumoniae promoted the accumulation of CD163+ macrophages in the adenomatous crypts to create an immunosuppressive niche, which not only accommodated the extended stay for its own sake but also deteriorated colorectal tumorigenesis. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1949-0976 1949-0984 19490976 |
Relation: | https://doaj.org/toc/1949-0976; https://doaj.org/toc/1949-0984 |
DOI: | 10.1080/19490976.2021.1980348 |
URL الوصول: | https://doaj.org/article/333f7a1ad7c84db085147ea7f20359fc |
رقم الأكسشن: | edsdoj.333f7a1ad7c84db085147ea7f20359fc |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 19490976 19490984 |
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DOI: | 10.1080/19490976.2021.1980348 |