Sepsis remains a leading cause of morbidity and mortality in critically ill patients, posing a major challenge to modern medicine. Despite advancements in treatment, the complexity of sepsis—characterized by a dysregulated immune response to infection—continues to resist definitive therapeutic solutions. Central to this challenge is the delicate balance between pro-inflammatory and anti-inflammatory responses, which can either clear pathogens or lead to damaging immunopathology. Recent research has highlighted the critical role of endogenous regulators in modulating innate immunity during sepsis. These naturally occurring molecules have the potential to either amplify or suppress immune responses, influencing the progression of the disease.

This Research Topic is dedicated to exploring the diverse and intricate roles of these endogenous regulators, offering new perspectives on their potential as therapeutic targets or agents. Targeted therapies that enhance the beneficial effects of these molecules or inhibit their detrimental actions could represent a pivotal advancement in the management of sepsis. The contributions in this special issue serve to highlight the complex interplay between the innate immune system and the molecules that regulate its function.

We invite research and review articles that span a broad range of topics, from basic mechanistic insights to translational research, to discuss the role of endogenous regulators of innate immunity in sepsis. These endogenous regulators include but not limited to:

• Macrophage cell surface hemichannel molecules (e.g., Connexin 43, pannexin 1, and others)
• Cytokines (e.g., IL-17, IL-33, IL-36, IL-37, IL-38, procathepsin).
• Stress-inducible proteins, such as heat shock proteins and Sestrin-2.
• Damage-associated molecular pattern molecules (DAMPs) like HMGB1, CIRP, SQSTM1, and others.
• Antimicrobial peptides
• Metabolic reprogramming, such as shifts in glycolysis and fatty acid oxidation, and metabolic products (e.g., lactate and lipids).
• Non-coding RNAs

This Research Topic aims to provide a comprehensive overview of current knowledge and inspire further research and innovation in this critical area of medicine.

Submit your idea

Impact

Frontiers in Immunology

Submit your idea

Impact