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

  1. Christopher P Arnold
  2. M Shane Merryman
  3. Alisha Harris-Arnold
  4. Sean A McKinney
  5. Chris W Seidel
  6. Sydney Loethen
  7. Kylie N Proctor
  8. Alejandro Sánchez Alvarado  Is a corresponding author
  1. Stowers Institute for Medical Research, United States
  2. University of Missouri, United States
  3. Pittsburg State University, United States

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. 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.

Article and author information

Author details

  1. Christopher P Arnold

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    No competing interests declared.
  2. M Shane Merryman

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    No competing interests declared.
  3. Alisha Harris-Arnold

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    No competing interests declared.
  4. Sean A McKinney

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    No competing interests declared.
  5. Chris W Seidel

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    No competing interests declared.
  6. Sydney Loethen

    University of Missouri, Kansas City, United States
    Competing interests
    No competing interests declared.
  7. Kylie N Proctor

    Pittsburg State University, Pittsburg, United States
    Competing interests
    No competing interests declared.
  8. Alejandro Sánchez Alvarado

    Stowers Institute for Medical Research, Kansas City, United States
    For correspondence
    asa@stowers.org
    Competing interests
    Alejandro Sánchez Alvarado, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1966-6959

Funding

Howard Hughes Medical Institute

  • Alejandro Sánchez Alvarado

National Institute of General Medical Sciences (R37GM057260)

  • Alejandro Sánchez Alvarado

Stowers Institute for Medical Research

  • Alejandro Sánchez Alvarado

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Richard Losick, Harvard University, United States

Publication history

  1. Received: April 8, 2016
  2. Accepted: July 19, 2016
  3. Accepted Manuscript published: July 21, 2016 (version 1)
  4. Accepted Manuscript updated: July 28, 2016 (version 2)
  5. Version of Record published: August 22, 2016 (version 3)

Copyright

© 2016, Arnold et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Christopher P Arnold
  2. M Shane Merryman
  3. Alisha Harris-Arnold
  4. Sean A McKinney
  5. Chris W Seidel
  6. Sydney Loethen
  7. Kylie N Proctor
  8. Alejandro Sánchez Alvarado
(2016)
Pathogenic shifts in endogenous microbiota impede tissue regeneration via distinct activation of TAK1/MKK/p38
eLife 5:e16793.
https://doi.org/10.7554/eLife.16793

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