The Role of Inflammasomes in LPS and Gram-Negative Bacterial Sepsis
Abstract
1. Introduction
2. Inflammasomes in Host Defense
3. Inflammasomes in Sepsis Induced by LPS
4. Inflammasomes in Bacterial Sepsis
5. Therapies with Immunomodulatory Effects in Sepsis
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
Abbreviations
DAMPs | Damage-associated molecular patterns |
PAMPs | Pathogen-associated molecular patterns |
LPS | Lipopolysaccharide |
NETs | Neutrophil extracellular traps |
GsdmD | Gasdermin D |
HMGB1 | High Mobility Group Box 1 |
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Inflammasome-Derived DAMPs | Action in LPS and Bacterial Sepsis Leading to Lethality |
---|---|
Hepatocyte-derived HMGB1 | Promotes internalization of LPS into macrophages and endothelial cells via RAGE receptor, activation of caspase-11, and lethality in mice. Neutralizing HMGB1 or hmgb1-deficient mice were protected from polymicrobial sepsis and endotoxemia [51]. HMGB1 induces DIC [52]. |
Histones | Induce endothelial dysfunction, hemorrhage, and thrombosis in LPS and polymicrobial sepsis. Lethality was reduced in mice by neutralizing antibodies to H4 or activated protein C (APC) [52,53]. |
NETs | LPS and bacteria induce NETs extrusion in neutrophils. NETs cause platelet- and erythrocyte-aggregation, fibrin deposition, and thrombosis leading to DIC in mice. Removal of NETs with a DNase infusion coagulation and improved tissue perfusion [52,54,55]. |
Tissue Factor (TF) | LPS induces non-canonical inflammasome activation and phosphatidylserine (PS) exposure, resulting in TF activation and DIC. Neutralization of TF and PS prevents LPS-induced DIC and reduces mortality in mice [56,57,58,59]. |
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Hernández-Cuellar, E.; Tsuchiya, K.; Medina-Contreras, O.; Valle-Ríos, R. The Role of Inflammasomes in LPS and Gram-Negative Bacterial Sepsis. J. Clin. Med. 2025, 14, 7102. https://doi.org/10.3390/jcm14197102
Hernández-Cuellar E, Tsuchiya K, Medina-Contreras O, Valle-Ríos R. The Role of Inflammasomes in LPS and Gram-Negative Bacterial Sepsis. Journal of Clinical Medicine. 2025; 14(19):7102. https://doi.org/10.3390/jcm14197102
Chicago/Turabian StyleHernández-Cuellar, Eduardo, Kohsuke Tsuchiya, Oscar Medina-Contreras, and Ricardo Valle-Ríos. 2025. "The Role of Inflammasomes in LPS and Gram-Negative Bacterial Sepsis" Journal of Clinical Medicine 14, no. 19: 7102. https://doi.org/10.3390/jcm14197102
APA StyleHernández-Cuellar, E., Tsuchiya, K., Medina-Contreras, O., & Valle-Ríos, R. (2025). The Role of Inflammasomes in LPS and Gram-Negative Bacterial Sepsis. Journal of Clinical Medicine, 14(19), 7102. https://doi.org/10.3390/jcm14197102