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Daniel Younger, PhD
Pronouns
He/Him/His
Job Title
Research Fellow
Academic Rank
Research Fellow
Department
Surgery
Authors
Daniel Younger, Hui Lin, Laura Cahill, Fei Guo, Alec Griffith, Brandon Hancock, Kaitlyn Howard, Josh Keegan, Mark Perrela, James Lederer
Principal Investigator
James Lederer
Research Category: Allergy, Immunology, Inflammation, and Infectious Diseases
Tags
Objective: Investigate how depleting or expanding Tregs in a mouse injury model influences the antimicrobial response to lung infection.
Methods: Treg populations in FoxP3 DTR and C57BL/6 mice were depleted by Diphtheria toxin (DT) or expanded using a Death Receptor 3 (DR3) agonist antibody. Mice underwent 25% body surface burn injury. Two days post, mice were inoculated with P. aeruginosa. Survival was monitored for 7 days. Bacterial clearance, organ injury, and plasma cytokines concentrations were measured at 24 hours.
Results: Depletion of Tregs led to decreased survivability, while expansion of Tregs enhanced survival following infection after burn injury. The depletion showed a reduction in the ability to clear bacteria from the lungs. Enrichment of Tregs had no effect on bacterial clearance. Organ injury levels were highest in burn injured Treg depleted mice, while organ injury was reduced in Treg expanded animals. Following infection proinflammatory cytokine levels increase, while anti-inflammatory cytokine levels decreased in plasma. Burn injury reduced cytokine production in response to infection. Expansion of Tregs after burn injury partially restored the cytokine response to infection.
Conclusion: These results indicate they play a central role in controlling immune homeostasis following injury and increases the tolerance to bacterial infections and sepsis.
Background: Opportunistic infections are a common complication of traumatic injuries and is one of the leading causes of mortality. This complication is in part due to inflammatory immune dysfunction following injury. We have previously shown that CD4+ regulatory T cells (Tregs) are responsive to injury and expand, which suggests they may play a role in controlling immune response to injury.
Objective: Investigate how depleting or expanding Tregs in a mouse injury model influences the antimicrobial response to lung infection.
Results: Depletion of Tregs after injury followed by infection led to decreased survivability, reduction in the ability to clear bacteria, and increased organ injury. Enrichment of Tregs showed increased survival, decreased organ injury, and no change ability to clear bacteria from the lungs. Burn injury reduces the inflammatory response to infection. Expansion of Tregs after burn injury partially restored the proinflammatory response to infection.
Conclusion: These findings indicate that the enhanced survival rate Treg expanded mice is likely due to the decreased levels of organ injury, and not due to the ability to clear the infection. These results indicate Tregs they play a central role in controlling immune regulation following injury and increases the tolerance to bacterial infections and sepsis.
