title: Pathogenic shifts in endogenous microbiota impede tissue regeneration via distinct activation of TAK1/MKK/p38.
abstract: 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.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Arnold
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: M Shane
authors.initials: MS
authors.lastname: Merryman
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Aleishia
authors.initials: A
authors.lastname: Harris-Arnold
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Sean A
authors.initials: SA
authors.lastname: McKinney
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Chris W
authors.initials: CW
authors.lastname: Seidel
authors.affiliation: University of Missouri, Columbia, United States.
authors.forename: Sydney
authors.initials: S
authors.lastname: Loethen
authors.affiliation: Pittsburg State University, Pittsburg, United States.
authors.forename: Kylie N
authors.initials: KN
authors.lastname: Proctor
authors.affiliation: Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Longhua
authors.initials: L
authors.lastname: Guo
authors.affiliation: Howard Hughes Medical Institute, Stowers Institute for Medical Research, Kansas City, United States.
authors.forename: Alejandro
authors.identifier: 0000-0002-1966-6959
authors.initials: A
authors.lastname: Sánchez Alvarado
mesh_terms: D000818:Animals; D017209:Apoptosis; D000069196:Gastrointestinal Microbiome; D020935:MAP Kinase Signaling System; D010986:Platyhelminths / Q000382:microbiology* / Q000502:physiology*; D012038:Regeneration
keywords: developmental biology; dysbiosis; infectious disease; innate immune system; microbiology; microbiome; planaria; regeneration; stem cells