Altered Gene Expression Profiles and Immune Responses in a Murine Model of a Non-lethal Flame Burn with Pseudomonas aeruginosa Infection
dc.contributor.author | Kambouris, Adrienne Renee | |
dc.date.accessioned | 2024-03-21T14:18:30Z | |
dc.date.available | 2024-03-21T14:18:30Z | |
dc.date.issued | 2023 | |
dc.identifier.uri | http://hdl.handle.net/10713/21567 | |
dc.description | University of Maryland, Baltimore School of Medicine. Ph.D. 2023. | en_US |
dc.description.abstract | Humanity has lived with fires for millennia, but combat, domestic use, and recent wildfires have increased the risk of burn injuries. Worldwide, over 100,000 deaths occur each year due to burns. If these patients survive the burn wound itself, the most common causes of death are multiorgan failure and sepsis, often caused by infection by Pseudomonas aeruginosa (PA). Utilizing a 10% total body surface area (TBSA) non-lethal flame burn model in mice, a superimposed infection of PA caused 100% mortality within 36 hours post-burn. This effect was transient, as infection 72 hours post-burn resulted in survival. The hypothesis was that this mortality could be linked to changes in gene expression that altered host-pathogen interaction. NanoString™, a system that allowed us to develop a custom panel of probes, was utilized to measure Mus musculus and PA gene transcripts simultaneously in each sample. Sampling from the blood, spleen, liver, and skin, gene expression in the burn and infection condition (B/I) was significantly different in each tissue when compared to mice that were burned alone, infected alone, and neither burned nor infected (Sham). The expression of the anti-inflammatory gene, Il10 is significantly increased over time in the spleen; administering anti-IL-10 antibodies delayed mortality by one day. While Arg1 and Nos2 gene expression were not significantly altered, administering arginine concurrently with PA restored survival in our mouse model, likely due to an inhibition of both PA motility and growth. We also hypothesized that burn-induced neutrophil dysfunction allowed for PA proliferation. Neutrophils isolated from the seroma of burned mice had a decreased ability to produce antibacterial reactive oxygen species (ROS) compared to neutrophils in the circulation of the same mice. Surprisingly, naïve neutrophils in the circulation of burned mice had a decreased ability to kill PA, possibly due to their premature ROS production induced by a burn-generated DAMP, HMGB1, present in the serum of burned but not Sham mice. In conclusion, a non-lethal burn injury is sufficient to induce multi-faceted changes in the murine immune system that results in an increased susceptibility to lethal PA superinfection. | en_US |
dc.language.iso | en_US | en_US |
dc.subject.mesh | Burns | en_US |
dc.subject.mesh | Gene Expression | en_US |
dc.subject.mesh | Pseudomonas aeruginosa | en_US |
dc.subject.mesh | Neutrophils | en_US |
dc.title | Altered Gene Expression Profiles and Immune Responses in a Murine Model of a Non-lethal Flame Burn with Pseudomonas aeruginosa Infection | en_US |
dc.type | dissertation | en_US |
dc.date.updated | 2024-02-01T02:06:01Z | |
dc.language.rfc3066 | en | |
dc.contributor.advisor | Cross, Alan S. | |
refterms.dateFOA | 2024-03-21T14:18:32Z |