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

eLife

Alejandro Sánchez Alvarado¹  Kylie N Proctor²  Aleishia Harris-Arnold³  Sean A McKinney³  Christopher P Arnold³  M Shane Merryman³  Longhua Guo³  Chris W Seidel³  Sydney Loethen⁴ 

[1] Howard Hughes Medical Institute, Stowers Institute for Medical Research, Kansas City, United States;Pittsburg State University, Pittsburg, United States;Stowers Institute for Medical Research, Kansas City, United States;University of Missouri, Columbia, United States;

关键词: planaria;    microbiome;    regeneration;    dysbiosis;    innate immune system;   

DOI  :  10.7554/eLife.16793

来源: DOAJ

【 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. The 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.

【 授权许可】

Unknown