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Infection Induced Inflammation Impairs Wound Healing Through IL-1β Signaling

38 Pages Posted: 14 Jul 2023 Publication Status: Published

See all articles by Simone Shen

Simone Shen

University of Wisconsin - Madison - Department of Medical Microbiology and Immunology

Veronika Miskolci

University of Wisconsin - Madison - Department of Medical Microbiology and Immunology

Colin Dewey

University of Wisconsin - Madison - Department of Biostatistics and Medical Informatics

John-Demian Sauer

University of Wisconsin - Madison - Department of Medical Microbiology and Immunology

Anna Huttenlocher

University of Wisconsin - Madison - Department of Medical Microbiology and Immunology

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Abstract

Wound healing is impaired by infection; however, how microbe-induced inflammation modulates tissue repair remains unclear. We took advantage of the optical transparency of zebrafish and a genetically tractable microbe, Listeria monocytogenes, to probe the role of infection and inflammation in wound healing. We found a critical window of microbial clearance necessary to limit persistent inflammation and enable efficient wound repair. Infection with bacteria engineered to activate the inflammasome, LmPyro, induced persistent inflammation and impaired healing despite low bacterial burden. In contrast, infection with an anti-inflammatory, apoptosis inducing strain, Lm-Apo, had similar infectious burden but was associated with rapid wound repair. Inflammatory infections induced il-1b expression and blocking IL-1R signaling partially rescued wound healing in the presence of persistent infection. Taken together, our findings suggest that the dynamics of microbe-induced tissue inflammation impacts repair in complex tissue damage independent of bacterial load, with a critical early window for efficient tissue repair.

Note:
Funding Information: This work was supported by GM118027 (A.H.) and R21 AI159312 (AH), 1R01AI137070 and 1R21AI173738 (J.D.S.), and NIH K99GM138699 and AHA 17POST33410970 (V.M.).

Declaration of Interests: The authors declare no competing interests.

Ethical Approval Statement: All protocols using zebrafish in this study has been approved by the University of Wisconsin-Madison Research Animals Resource Center (protocol M005405-A02).

Keywords: Wound Healing, Infection, Inflammation, IL1b

Suggested Citation

Shen, Simone and Miskolci, Veronika and Dewey, Colin and Sauer, John-Demian and Huttenlocher, Anna, Infection Induced Inflammation Impairs Wound Healing Through IL-1β Signaling. Available at SSRN: https://ssrn.com/abstract=4507726 or http://dx.doi.org/10.2139/ssrn.4507726
This version of the paper has not been formally peer reviewed.

Simone Shen

University of Wisconsin - Madison - Department of Medical Microbiology and Immunology ( email )

Veronika Miskolci

University of Wisconsin - Madison - Department of Medical Microbiology and Immunology ( email )

Colin Dewey

University of Wisconsin - Madison - Department of Biostatistics and Medical Informatics ( email )

John-Demian Sauer

University of Wisconsin - Madison - Department of Medical Microbiology and Immunology ( email )

Anna Huttenlocher (Contact Author)

University of Wisconsin - Madison - Department of Medical Microbiology and Immunology ( email )

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