Mammalian target of rapamycin regulates a hyperresponsive state in pulmonary neutrophils late after burn injury.

Mammalian target of rapamycin regulates a hyperresponsive state in pulmonary neutrophils late after burn injury. J Leukoc Biol. 2018 Feb 02;: Authors: Dunn JLM, Kartchner LB, Gast K, Sessions M, Hunter RA, Thurlow L, Richardson A, Schoenfisch M, Cairns BA, Maile R Abstract Bacterial pneumonia is a leading cause of death late after burn injury due to the severe immune dysfunction that follows this traumatic injury. The Mechanistic/Mammalian Target of Rapamycin (mTOR) pathway drives many effector functions of innate immune cells required for bacterial clearance. Studies have demonstrated alterations in multiple cellular processes in patients and animal models following burn injury in which mTOR is a central component. Goals of this study were to (1) investigate the importance of mTOR signaling in antimicrobial activity by neutrophils and (2) therapeutically target mTOR to promote normalization of the immune response. We utilized a murine model of 20% total body surface area burn and the mTOR-specific inhibitor rapamycin. Burn injury led to innate immune hyperresponsiveness in the lung including recruitment of neutrophils with greater ex vivo oxidative activity compared with neutrophils from sham-injured mice. Elevated oxidative function correlated with improved clearance of Pseudomonas aeruginosa, despite down-regulated expression of the bacterial-sensing TLR molecules. Rapamycin administration reversed the burn injury-induced lung inn...
Source: Journal of Leukocyte Biology - Category: Hematology Authors: Tags: J Leukoc Biol Source Type: research