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Immunometabolic Circuits in Infection for Advancing Host Directed Therapies
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Metabolic programs define dysfunctional immune responses in severe COVID-19 patients
Elizabeth A Thompson1,2, Katherine Cascino3, Alvaro A Ordonez4
1Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Medrxiv : the Preprint Server for Health Sciences
|September 16, 2020
Summary
Severe COVID-19 involves unique immune cell metabolic changes. Researchers identified specific T cells and myeloid-derived suppressor cells (MDSCs) linked to disease severity, offering potential therapeutic targets.
Area of Science:
- Immunology
- Metabolomics
- Cell Biology
Background:
- Understanding immune dysregulation in severe COVID-19 is crucial for patient outcomes.
- Distinct immune-metabolic programs differentiate severe disease from recovery or other viral infections.
Approach:
- A novel assay was used to analyze immune-metabolic programs in T cells and myeloid cells from severe and recovered COVID-19 patients.
- High-resolution microscopy and molecular techniques identified unique cell populations and their metabolic characteristics.
Key Points:
- Expanded T cells with high H3K27me3 and voltage-dependent anion channel (VDAC) expression were found in severe COVID-19, associated with mitochondrial dysfunction and apoptosis.
- Hexokinase II+ polymorphonuclear-myeloid derived suppressor cells (PMN-MDSCs) and carnitine palmitoyltransferase 1a (CPT1a)+ monocytic MDSCs (M-MDSCs) expressing VDAC were specific to severe COVID-19.
- These cellular phenotypes, particularly M-MDSCs, could distinguish severe from mild disease and were more prevalent in elderly patients, correlating with lymphopenia.
Conclusions:
- Novel immune-metabolic phenotypes in T cells and myeloid-derived suppressor cells are characteristic of severe COVID-19.
- These findings offer insights into immune dysfunction and provide potential biomarkers for disease severity prediction.
- Targeting these metabolic pathways presents opportunities for novel therapeutic interventions in severe COVID-19.
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