ABSTRACT
The international biomedical community has been currently facing a need to find a simple and most accessible type of analysis that helps to diagnose tuberculosis (TB) with the maximum reliability even before the onset of clinical manifestations. Tuberculosis results in more deaths than any other pathogen, second only to pneumonia caused by the SARS-CoV-2 virus, but the majority of infected people remain asymptomatic. In addition, it is important to develop methods to distinguish various forms of tuberculosis infection course at early stages and to reliably stratify patients into appropriate groups (persons with a rapidly progressing infection, chronic course, latent infection carriers). Immunometabolism investigates a relationship between bioenergetic pathways and specific functions of immune cells that has recently become increasingly important in scientific research. The host anti-mycobacteria immune response in tuberculosis is regulated by a number of metabolic networks that can interact both cooperatively and antagonistically, influencing an outcome of the disease. The balance between inflammatory and immune reactions limits the spread of mycobacteria in vivo and protects from developing tuberculosis. Cytokines are essential for host defense, but if uncontrolled, some mediators may contribute to developing disease and pathology. Differences in plasma levels of metabolites between individuals with advanced infection, LTBI and healthy individuals can be detected long before the onset of the major related clinical signs. Changes in amino acid and cortisol level may be detected as early as 12 months before the onset of the disease and become more prominent at verifying clinical diagnosis. Assessing serum level of certain amino acids and their ratios may be used as additional diagnostic markers of active pulmonary TB. Metabolites, including serum fatty acids, amino acids and lipids may contribute to detecting active TB. Metabolic profiles indicate about increased indolamine 2.3-di-oxygenase 1 (IDO1) activity, decreased phospholipase activity, increased adenosine metabolite level, and fibrous lesions in active vs. latent infection. TB treatment can be adjusted based on individual patient metabolism and biomarker profiles. Thus, exploring immunometabolism in tuberculosis is necessary for development of new therapeutic strategies. Copyright © 2022 Saint Petersburg Pasteur Institute. All rights reserved.
ABSTRACT
Background: Monocytes and macrophages drive the inflammatory response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) and they are a major source of eicosanoids in airway inflammation. Method: We used RNA sequencing and LC-MS/ MS analysis to determine transcriptional and lipid mediator profiles of monocyte-derived macrophages from convalescent COVID-19 patients 3-5 months post-SARS- CoV- 2 infection. Results: We found that monocyte-derived macrophages (MDM) from SARS-CoV- 2- infected individuals with mild disease show an inflammatory transcriptional and metabolic imprint several (3-5) months after SARS-CoV- 2 infection. MDM from convalescent SARS-CoV- 2- infected individuals showed higher expression of fatty acid-metabolic enzymes and increased production of pro-inflammatory eicosanoids, particularly neutrophil chemotactic leukotriene B4 (LTB4) and LTD4 a driver of airway remodeling. MDM from previously SARS-CoV- 2- infected subjects showed an exaggerated induction of inflammatory chemokines as well as T-cell suppressive enzymes and receptors following stimulation with spike protein or LPS. Corticosteroids reduced inflammatory cytokine-, but increased leukotriene production in macrophages. Conclusion: Thus, SARS-CoV- 2 infection leaves an inflammatory imprint in the monocyte/macrophage compartment that drives aberrant effector functions and eicosanoid metabolism, possibly explaining long-term effects in patients recovering from mild COVID-19.