Pathogenic shifts in endogenous microbiota impede tissue regeneration via distinct activation of TAK1/MKK/p38

被引：75

作者：

Arnold, C. P. ^{[1
]}

Merryman, M. S. ^{[1
]}

Harris-Arnold, A. ^{[1
]}

McKinney, S. A. ^{[1
]}

Seidel, C. W. ^{[1
]}

Loethen, S. ^{[3
]}

Proctor, K. N. ^{[2
]}

Guo, L. ^{[1
]}

Alvarado, Sanchez A. ^{[1
,4
]}

机构：

[1] Stowers Inst Med Res, Kansas City, MO 64110 USA

[2] Pittsburg State Univ, Kansas City, MO USA

[3] Univ Missouri, Kansas City, MO 64110 USA

[4] Howard Hughes Med Inst, Kansas City, MO USA

来源：

ELIFE | 2016年 / 5卷

关键词：

DROSOPHILA HOST-DEFENSE; DOUBLE-STRANDED-RNA; CELL-DEATH; PLANARIAN REGENERATION; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; GUT MICROBIOTA; STEM-CELLS; INFLAMMATION; PATHWAY;

D O I：

10.7554/eLife.16793

中图分类号：

Q [生物科学];

学科分类号：

090105 [作物生产系统与生态工程];

摘要：

The interrelationship between endogenous microbiota, the immune system, and tissue regeneration is an area of intense research due to its potential therapeutic applications. We investigated this relationship in Schmidtea mediterranea, a model organism capable of regenerating any and all of its adult tissues. Microbiome characterization revealed a high Bacteroidetes to Proteobacteria ratio in healthy animals. Perturbations eliciting an expansion of Proteobacteria coincided with ectopic lesions and tissue degeneration. Culture of these bacteria yielded a strain of Pseudomonas capable of inducing progressive tissue degeneration. RNAi screening uncovered a TAK1 innate immune signaling module underlying compromised tissue homeostasis and regeneration during infection. TAK1/MKK/p38 signaling mediated opposing regulation of apoptosis during infection versus normal tissue regeneration. Given the complex role of inflammation in either hindering or supporting reparative wound healing and regeneration, this invertebrate model provides a basis for dissecting the duality of evolutionarily conserved inflammatory signaling in complex, multi-organ adult tissue regeneration.

引用

页数：71

共 75 条

[1]

Programmed cell death mediated by ced-3 and ced-4 protects Caenorhabditis elegans from Salmonella typhimurium-mediated killing [J].