Murine leukocyte dysfunction in response to a non-lethal flame burn.

Area of Science:

• Immunology
• Wound Healing
• Microbiology

Background:

• Burn injuries can compromise host immunity, increasing susceptibility to infections like Pseudomonas aeruginosa (PA).
• Seroma formation under burn wounds sequesters immune cells, potentially affecting their function.
• Leukocyte dysfunction is implicated in impaired host defense following burns and infection.

Purpose of the Study:

• To investigate the functional status of leukocytes in a mouse model of burn injury and PA infection.
• To determine the impact of seroma fluid on leukocyte antimicrobial activity.
• To explore the role of serum components and danger-associated molecular patterns (DAMPs) in leukocyte activation and dysfunction.

Main Methods:

• Utilized a non-lethal, 10% total body surface area flame burn mouse model with PA infection.
• Isolated leukocytes from circulation and seroma fluid for functional assays (PA killing, reactive oxygen species production).
• Incubated leukocytes with seroma fluid and serum from burned/infected mice to assess in vitro effects.

Main Results:

• Leukocytes from burned mice exhibited reduced ability to kill PA compared to controls.
• Seroma fluid incubation impaired the killing capacity of both Sham and burned mouse leukocytes.
• Leukocytes from seroma showed decreased reactive oxygen species (ROS) production compared to circulating leukocytes.
• Serum from burned mice induced resting ROS production in Sham leukocytes, potentially linked to HMGB1.

Conclusions:

• A non-lethal burn prematurely activates circulating leukocytes, compromising their function at the infection site.
• The burn wound microenvironment, specifically seroma fluid, further inhibits leukocyte function.
• Impaired leukocyte activity contributes to a weakened immune response, leading to increased mortality from sepsis post-burn and infection.