Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2S2, Canada.
Department of Immunology & Microbiology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
Cell Rep. 2020 Jan 28;30(4):1088-1100.e5. doi: 10.1016/j.celrep.2019.12.094.
Pathogen-mediated damage to the intestinal epithelium activates compensatory growth and differentiation repair programs in progenitor cells. Accelerated progenitor growth replenishes damaged tissue and maintains barrier integrity. Despite the importance of epithelial renewal to intestinal homeostasis, we know little about the effects of pathogen-commensal interactions on progenitor growth. We find that the enteric pathogen Vibrio cholerae blocks critical growth and differentiation pathways in Drosophila progenitors, despite extensive damage to epithelial tissue. We show that the inhibition of epithelial repair requires interactions between the Vibrio cholerae type six secretion system and a community of common symbiotic bacteria, as elimination of the gut microbiome is sufficient to restore homeostatic growth in infected intestines. This work highlights the importance of pathogen-symbiont interactions for intestinal immune responses and outlines the impact of the type six secretion system on pathogenesis.
病原体对肠道上皮的损伤激活了祖细胞中的代偿性生长和分化修复程序。加速的祖细胞生长补充受损组织并维持屏障完整性。尽管上皮更新对于肠道内稳态很重要，但我们对病原体-共生体相互作用对祖细胞生长的影响知之甚少。我们发现，尽管肠道上皮组织受到广泛损伤，但肠道病原体霍乱弧菌仍能阻断果蝇祖细胞中关键的生长和分化途径。我们表明，上皮修复的抑制需要霍乱弧菌的 VI 型分泌系统与一组常见共生细菌之间的相互作用，因为消除肠道微生物组足以恢复感染肠道中的稳态生长。这项工作强调了病原体-共生体相互作用对肠道免疫反应的重要性，并概述了 VI 型分泌系统对发病机制的影响。
