Project 2: Role of mTOR/PPAR Axis

Determine the role and associated mechanisms of mTOR/PPAR axis in the innate immune cell pathophysiology observed after burn and inhalation injury responsible for susceptibility to secondary infection.

Burn injury and inhalation injury generates damage and release of numerous inflammatory stimuli (Damage-Associated Molecular Patterns (DAMPs)) that resident innate immune cells (neutrophil and macrophages) and non-canonical immune responder cells (such as pulmonary epithelial cells) bind to through Pattern Recognition Receptors (PRR) including Toll-Like Receptors (TLR). We have found that this DAMP-TLR interaction results in the activation of the Mechanistic/Mammalian Target of Rapamycin (mTOR) pathway which drives many metabolic and immune, including those associated with glycolysis driven pro-inflammatory cytokine expression which results in recruitment and activation of immune cells promoting exacerbated tissue damage.

Selected References:

Hall HR, Mahung C, Dunn JLM, Kartchner LM, Seim RF, Cairns BA, Wallet SM, Maile R. Characterization of the Basal and mTOR-Dependent Acute Pulmonary and Systemic Immune Response in a Murine Model of Combined Burn and Inhalation Injury. Int J Mol Sci. 2022 Aug 7;23(15):8779. PMID: 35955914

Dunn JLM, Kartchner LB, Gast K, Sessions M, Hunter RA, Thurlow L, Richardson A, Schoenfisch M, Cairns BA, Maile R, “Mammalian target of rapamycin regulates a hyperresponsive state in pulmonary neutrophils late after burn injury” J Leukoc Biol. 2018 May;103(5):909-918 PMID: 29393976