Antibiotics-induced gut microbiota dysbiosis promotes tumor initiation via affecting APC-Th1 development in mice
| Autor: | Dongsheng Zhai, Zifan Lu, Zicheng Ye, Ming Wei, Ting Xue, Shan Wang, Li Wang, Chengming Xu, Banjun Ruan, Yinghao Jiang, Huanyu Lu, Zhenyu Wang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides T cell Injections Subcutaneous Adenomatous Polyposis Coli Protein Biophysics Administration Oral Tumor initiation Gut flora digestive system Biochemistry 03 medical and health sciences Mice 0302 clinical medicine Immune system Cell Line Tumor medicine Animals Antigen-presenting cell Molecular Biology Melanoma Cell Proliferation biology Cell Biology Th1 Cells biology.organism_classification medicine.disease Primary tumor Anti-Bacterial Agents Gastrointestinal Microbiome Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Cytokines Tumor necrosis factor alpha Female Dysbiosis |
| Zdroj: | Biochemical and biophysical research communications. 488(2) |
| ISSN: | 1090-2104 |
| Popis: | Gut microbiota is critical for maintaining body immune homeostasis and thus affects tumor growth and therapeutic efficiency. Here, we investigated the link between microbiota and tumorgenesis in a mice model of subcutaneous melanoma cell transplantation, and explored the underlying mechanism. We found disruption of gut microbiota by pretreating mice with antibiotics promote tumor growth and remodeling the immune compartment within the primary tumor. Indeed, gut microbial dysbiosis reduced the infiltrated mature antigen-presenting cells of tumor, together with lower levels of co-stimulators, such as CD80, CD86 and MHCII, as well as defective Th1 cytokines, including IFNγ, TNFα, IL12p40, and IL12p35. Meantime, splenic APCs displayed blunted ability in triggering T cell proliferation and IFNγ secretion. However, oral administration of LPS restored the immune surveillance effects and thus inhibited tumor growth in the antibiotics induced gut microbiota dysbiosis group. Taken together, these data highly supported that antibiotics induced gut microbiota dysbiosis promotes tumor initiation, while LPS supplementation would restore the effective immune surveillance and repress tumor initiation. |
| Databáze: | OpenAIRE |
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