Overview

Science Advances has published an article discussing the role of neutrophil and programmed death ligand 1 (PD-L1) pathways in wound healing of a burn injury.

Below are some highlighted topics from the article:

• Importance of proactive infection control in burn injury
• Role of neutrophils in a burn injury
• Programmed death ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) immune checkpoint pathway in inflammation regulation
• PD-L1 pathway in wound healing of a burn injury

Importance of proactive infection control in burn injury

  • According to an article published by Clinical Infectious Diseases, approximately 40,000 burn injuries required hospitalization in the United States in 2016.
  • Burn injury has been correlated to acute respiratory distress syndrome (ARDS).
  • ARDS makes patients with burn injury an increased risk of bacterial pneumonia.

Role of neutrophils in a burn injury

  • Neutrophils have a critical role in the healing process, beyond the traditional role in regulating infection.
  • Upon skin-associated burn injury, neutrophils are let out from the bone marrow.
  • Fixed cells let out inflammatory cytokines and chemokines to engage in repairing neutrophils to the injury site.
  • In the bloodstream, neutrophils are stimulated by transforming growth factor beta (TGF-beta) and they start to express PD-L1.
  • If neutrophils are not able to migrate toward the injury site, a delay in the resurfacing of a wound with new epithelium is shown.

PD-L1 and PD-1 immune checkpoint pathway in inflammation regulation

  • PD-L1 and PD-1 immune checkpoint pathways avoid exaggerated tissue destruction during inflammation.
  • PD-L1 is expressed by multiple cell types.
  • PD-L1 expression is encouraged by various proinflammatory factors.
  • PD-L1 expression on neutrophils elevates with inflammation and corresponds with weakened antibacterial function during sepsis.

PD-L1 pathway in wound healing of a burn injury

  • Exosomal PD-L1 has been shown to advance skin cell migration and wound healing.
  • In the mice model, scientists identified a population of neutrophils that temporarily elevate the expression of PD-L1 following burn injury.
  • The population of neutrophils is retained in the lung.
  • Scientists identified that neutrophils act an important role in balancing wound repair and mice’s susceptibility to lung infection during burn injury.
  • Blockade of either PD-L1 or TGF-beta decreases the neutrophil burden in the lung and at the same time defends mice from a lung infection.
  • Neutralization of TGF-beta helps wound healing following burn injury.
  • Scientists found out different roles for anti-PD-L1 and anti-TGF-beta monoclonal antibodies:
    • When an anti-PD-L1 antibody is present, neutrophils no longer stop in the lung but move quickly to the skin
    • TGF-beta neutralization decreases neutrophil aggregation in the lung but neutrophil migration to the skin is unaffected

Reference:

1. Ajitha Thanabalasuriar, Abby J. Chiang, Christopher Morehouse, Margarita Camara,  Shonda Hawkins, Ashley E. Keller, Adem C. Koksal, Carolina S. Caceres, Aaron A. Berlin, Nicholas Holoweckyj, Virginia N. Takahashi, Lily Cheng, Melissa de los Reyes, Mark Pelletier, Andriani C. Patera, Bret Sellman, Sonja Hess, Marcello Marelli, Chelsea C. Boo, Taylor S. Cohen, Antonio DiGiandomenico. PD-L1+ neutrophils contribute to injury-induced infection susceptibility. Science Advance. 2021 Mar 5. DOI: 10.1126/sciadv.abd9436.

2. Anne M. Lachiewicz, Christopher G. Hauck, David J. Weber, Bruce A. Cairns, David van Duin. Bacterial Infections After Burn Injuries: Impact of Multidrug Resistance. Clinical Infectious Diseases. 2017 Dec 15. DOI: 10.1093/cid/cix682

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