PMID- 35955914 OWN - NLM STAT- MEDLINE DCOM- 20220815 LR - 20220831 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 23 IP - 15 DP - 2022 Aug 7 TI - Characterization of the Basal and mTOR-Dependent Acute Pulmonary and Systemic Immune Response in a Murine Model of Combined Burn and Inhalation Injury. LID - 10.3390/ijms23158779 [doi] LID - 8779 AB - Severe burn injury leads to a cascade of local and systemic immune responses that trigger an extreme state of immune dysfunction, leaving the patient highly susceptible to acute and chronic infection. When combined with inhalation injury, burn patients have higher mortality and a greater chance of developing secondary respiratory complications including infection. No animal model of combined burn and inhalation injury (B+I) exists that accurately mirrors the human clinical picture, nor are there any effective immunotherapies or predictive models of the risk of immune dysfunction. Our earlier work showed that the mechanistic/mammalian target of rapamycin (mTOR) pathway is activated early after burn injury, and its chemical blockade at injury reduced subsequent chronic bacterial susceptibility. It is unclear if mTOR plays a role in the exacerbated immune dysfunction seen after B+I injury. We aimed to: (1) characterize a novel murine model of B+I injury, and (2) investigate the role of mTOR in the immune response after B+I injury. Pulmonary and systemic immune responses to B+I were characterized in the absence or presence of mTOR inhibition at the time of injury. Data describe a murine model of B+I with inhalation-specific immune phenotypes and implicate mTOR in the acute immune dysfunction observed. FAU - Hall, Hannah R AU - Hall HR AD - Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. AD - North Carolina Jaycee Burn Center, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Mahung, Cressida AU - Mahung C AD - North Carolina Jaycee Burn Center, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Dunn, Julia L M AU - Dunn JLM AD - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Kartchner, Laurel M AU - Kartchner LM AD - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Seim, Roland F AU - Seim RF AUID- ORCID: 0000-0001-9023-4502 AD - North Carolina Jaycee Burn Center, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. AD - Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Cairns, Bruce A AU - Cairns BA AD - North Carolina Jaycee Burn Center, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. AD - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. FAU - Wallet, Shannon M AU - Wallet SM AD - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. AD - Division of Oral and Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC 27599, USA. FAU - Maile, Robert AU - Maile R AUID- ORCID: 0000-0002-9126-4188 AD - North Carolina Jaycee Burn Center, Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. AD - Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. AD - Curriculum in Toxicology and Environmental Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. LA - eng GR - R01 GM131124/GM/NIGMS NIH HHS/United States GR - R01GM131124/GM/NIGMS NIH HHS/United States GR - T32ES007126/ES/NIEHS NIH HHS/United States GR - 5T32GM008450/GM/NIGMS NIH HHS/United States PT - Journal Article DEP - 20220807 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - EC 2.7.1.1 (MTOR protein, human) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) SB - IM MH - Animals MH - *Burns/metabolism MH - Disease Models, Animal MH - Humans MH - Immunity MH - Immunotherapy MH - *Lung Injury/complications MH - Mammals MH - Mice MH - TOR Serine-Threonine Kinases PMC - PMC9368856 OTO - NOTNLM OT - burn injury OT - inhalation injury OT - mTOR COIS- The authors declare no conflict of interest. EDAT- 2022/08/13 06:00 MHDA- 2022/08/16 06:00 PMCR- 2022/08/07 CRDT- 2022/08/12 01:14 PHST- 2022/07/01 00:00 [received] PHST- 2022/07/26 00:00 [revised] PHST- 2022/08/04 00:00 [accepted] PHST- 2022/08/12 01:14 [entrez] PHST- 2022/08/13 06:00 [pubmed] PHST- 2022/08/16 06:00 [medline] PHST- 2022/08/07 00:00 [pmc-release] AID - ijms23158779 [pii] AID - ijms-23-08779 [pii] AID - 10.3390/ijms23158779 [doi] PST - epublish SO - Int J Mol Sci. 2022 Aug 7;23(15):8779. doi: 10.3390/ijms23158779.