Infection induced inflammation impairs wound healing through IL-1β signaling

Area of Science:

• Immunology
• Microbiology
• Regenerative Medicine

Background:

• Wound healing is a complex process susceptible to disruption by microbial infections.
• The precise mechanisms by which infection-induced inflammation affects tissue repair are not fully understood.
• Zebrafish offer a unique model for studying dynamic biological processes due to their optical transparency and genetic tractability.

Purpose of the Study:

• To investigate the role of infection-induced inflammation in modulating wound healing.
• To explore the impact of inflammasome activation by microbes on tissue repair dynamics.
• To identify critical factors influencing the interplay between infection, inflammation, and healing.

Main Methods:

• Utilized zebrafish as a model organism with transparent tissues.
• Employed genetically engineered Listeria monocytogenes (Lm-Pyro) to induce inflammasome activation.
• Assessed wound healing, inflammation markers (il1b expression), and IL-1R signaling blockade.
• Determined the effect of microbial clearance timing on healing outcomes.

Main Results:

• Infection with Lm-Pyro triggered persistent inflammation and impaired wound healing, irrespective of bacterial burden.
• Inflammatory infections led to increased il1b gene expression.
• Blocking IL-1 receptor (IL-1R) signaling partially restored wound healing during persistent infection.
• A critical early window for microbial clearance was identified as essential for limiting inflammation and promoting repair.

Conclusions:

• Microbe-induced inflammation significantly impacts complex tissue repair, independent of bacterial load.
• The dynamics of inflammation, particularly persistent inflammation, are detrimental to efficient wound healing.
• Targeting inflammatory pathways (e.g., IL-1R signaling) and ensuring timely microbial clearance are crucial for optimizing wound repair in infected tissues.