Transcriptomic Differences in Peripheral Monocyte Populations in Septic Patients Based on Outcome

Author:

Barrios Evan L.1,Rincon Jaimar C.1,Willis Micah2,Polcz Valerie E.1,Leary John3,Darden Dijoia B.1,Balch Jeremy A.1,Larson Shawn D.1,Loftus Tyler J.1,Mohr Alicia M.1,Wallet Shannon2,Brusko Maigan A.4,Balzano-Nogueira Leandro5,Cai Guoshuai1,Sharma Ashish6,Upchurch Gilbert R.6,Kladde Michael P.7,Mathews Clayton E.4,Maile Robert1,Moldawer Lyle L.1,Bacher Rhonda3,Efron Philip A.1

Affiliation:

1. Sepsis and Critical Illness Research Center, Department of Surgery, College of Medicine, Gainesville, FL, USA

2. Department of Oral Biology, College of Dentistry, Gainesville, FL, USA

3. Department of Biostatistics, College of Medicine, Gainesville, FL, USA

4. Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, Gainesville, FL, USA

5. Department of Microbiology and Cell Science, College of Medicine, Gainesville, FL, USA

6. Department of Surgery, College of Medicine, Gainesville, FL, USA

7. Department of Biochemistry and Molecular Biology, College of Medicine, Gainesville, FL, USA

Abstract

ABSTRACT Post-sepsis early mortality is being replaced by survivors who experience either a rapid recovery and favorable hospital discharge or the development of chronic critical illness (CCI) with suboptimal outcomes. The underlying immunological response that determines these clinical trajectories remains poorly defined at the transcriptomic level. As classical and non-classical monocytes are key leukocytes in both the innate and adaptive immune systems, we sought to delineate the transcriptomic response of these cell types. Using single-cell RNA sequencing and pathway analyses, we identified gene expression patterns between these two groups that are consistent with differences in TNFα production based on clinical outcome. This may provide therapeutic targets for those at risk for CCI in order to improve their phenotype/endotype, morbidity, and long-term mortality.

Publisher

Ovid Technologies (Wolters Kluwer Health)

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