Targeting Protein Post-Translational Modifications (PTMs) for Diagnosis and Treatment of Sepsis

Sepsis is an inflammatory disorder and a life-threatening organ dysfunction caused by dysregulated host response to microbial infection. Neutrophils and macrophages play pivotal roles in defense against sepsis. Neutrophils and macrophages exploit neutrophil extracellular traps (NETosis) and pyroptosis to sequester extracellular microbes or inactive intracellular pathogens. Moreover, the proteins released from these immune cells potentially serve as biomarkers for diagnosis of severe inflammation and sepsis. However, overreacted NETosis and pyroptosis can cause cytokine production, multiple organ damage and septic shock. It remains unknown how widespread NETosis and pyroptosis can perpetuate cytokine storm of sepsis and induce multiple organ dysfunction syndrome. Experimental evidence indicates that protein post-translational modifications (PTMs) are involved in governing NETosis and pyroptosis. Inhibition of histone deacetylase, palmitoyl acyltransferase, protein kinase, or peptidylarginine deiminase has shown to decrease pro-inflammatory cytokine production, increase immune cell activity, ameliorate organ damage, and improve survival in sepsis.

The pathogenesis of sepsis is variable and complex. Cellular and molecular mechanisms involved in the immunology of sepsis include: imbalance of inflammatory response, immune cell dysfunction, coagulopathy, immune network abnormalities, decreased phagocytosis, and other pathophysiological processes. It is unclear exactly how infection induces specific protein PTMs, and how the protein PTMs consequently modulate NETosis and pyroptosis, leading to inflammatory disorder, cytokine storm, disseminated intravascular coagulation (DIC), organ dysfunction, etc. 

This Research Topic aims to elucidate how protein PTMs modulate neutrophil and macrophage functions associated with sepsis. We welcome the submission of Original Research and Review articles that cover, but are not limited to, the following topics: 

• Modulation of protein PTMs in infection and immune response

• Cellular and molecular mechanisms of protein PTMs that govern the sepsis-induced abnormal phagocytosis and immunoparalysis

• Effect of protein PTMs on cytokine storm in Covid-19

• Protein PTMs-induced epigenetic and transcriptional reprogramming of immune cells in severe inflammation and/or infection

• Regulation of the phenotype of immune cells (neutrophils and macrophages) by protein PTMs

• Potential biomarkers derived from protein PTMs for diagnosis and prognosis of sepsis