Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Cell Host Microbe. 2010 Apr 22;7(4):265-276. doi: 10.1016/j.chom.2010.03.004.
The gastrointestinal tract harbors a diverse microbiota that has coevolved with mammalian hosts. Though most associations are symbiotic or commensal, some resident bacteria (termed pathobionts) have the potential to cause disease. Bacterial type VI secretion systems (T6SSs) are one mechanism for forging host-microbial interactions. Here we reveal a protective role for the T6SS of Helicobacter hepaticus, a Gram-negative bacterium of the intestinal microbiota. H. hepaticus mutants with a defective T6SS display increased numbers within intestinal epithelial cells (IECs) and during intestinal colonization. Remarkably, the T6SS directs an anti-inflammatory gene expression profile in IECs, and CD4+ T cells from mice colonized with T6SS mutants produce increased interleukin-17 in response to IECs presenting H. hepaticus antigens. Thus, the H. hepaticus T6SS limits colonization and intestinal inflammation, promoting a balanced relationship with the host. We propose that disruption of such balances contributes to human disorders such as inflammatory bowel disease and colon cancer.
胃肠道中栖息着多样化的微生物群落，这些微生物与哺乳动物宿主共同进化。虽然大多数微生物与宿主之间存在共生或共栖关系，但一些常驻细菌（称为条件致病菌）有可能引发疾病。细菌的 VI 型分泌系统（T6SS）是一种影响宿主-微生物相互作用的机制。在这里，我们揭示了肠道微生物群中革兰氏阴性菌——嗜胆菌属的 T6SS 具有保护作用。T6SS 缺陷的嗜胆菌属突变体在肠道上皮细胞（IEC）和肠道定植期间的数量增加。值得注意的是，T6SS 可在 IEC 中诱导抗炎基因表达谱，定植 T6SS 突变体的小鼠的 CD4+T 细胞在遇到呈现嗜胆菌属抗原的 IEC 时会产生更多的白细胞介素-17。因此，嗜胆菌属的 T6SS 可限制定植和肠道炎症，促进与宿主之间的平衡关系。我们提出，这种平衡的破坏可能导致人类疾病，如炎症性肠病和结肠癌。
