Related Experiment Video
Updated: May 15, 2026
Detection of Inflammasome Activation and Pyroptotic Cell Death in Murine Bone Marrow-derived Macrophages
Published on: May 21, 2018
Targeting inflammasome, IL-1β, and coagulation in melioidosis
1Department of Microbiology and Immunology, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States.
Abstract:
Burkholderia pseudomallei is a Gram-negative bacterium that causes melioidosis, a disease endemic in Southeast Asia and Northern Australia and increasingly detected in other tropical regions. B. pseudomallei is resistant to many antibiotics and no vaccine for melioidosis is currently available. The disease, particularly its pneumonic form, has high mortality, often due to sepsis. Accumulating evidence from our and other groups has shown that inflammasome and toll-like receptors (TLR) activation during B. pseudomallei lung infection causes an excessive inflammatory response that becomes deleterious due to damage to lung tissues. Interleukin (IL)-1β and neutrophils proteases appear to be particularly detrimental. Caspase-11 inflammasome activation has been shown to play a critical role in sepsis through activation of Tissue Factor and blood coagulation leading to disseminated intravascular coagulation. Sepsis and coagulopathy are serious complications in melioidosis suggesting that caspase-11 activation can be a pathogenic mechanism in this disease. Here, we discuss the potential therapeutic benefits of inhibitors of inflammasomes, IL-1β, neutrophil elastase, bradykinin and Tissue factor for melioidosis treatment.
Insights
Melioidosis, caused by Burkholderia pseudomallei, involves harmful inflammation and sepsis. Targeting inflammasomes, IL-1β, and neutrophil proteases may offer new treatments for this dangerous infection.
Area of Science:
- Infectious Diseases
- Immunology
- Pathophysiology
Background:
- * Burkholderia pseudomallei causes melioidosis, a serious tropical disease with high mortality, particularly the pneumonic form.
- * Current treatments are limited due to antibiotic resistance, and no vaccine is available.
- * Excessive inflammation mediated by inflammasomes and Toll-like receptors (TLRs) during infection damages lung tissue.
Purpose of the Study:
- * To explore the role of caspase-11 inflammasome activation in melioidosis-associated sepsis and coagulopathy.
- * To discuss the potential therapeutic benefits of targeting specific inflammatory pathways and molecules.
Main Methods:
- * Review of existing evidence on inflammasome and TLR activation in B. pseudomallei infection.
- * Analysis of the role of caspase-11 in sepsis and disseminated intravascular coagulation.
- * Discussion of potential therapeutic targets including inflammasomes, IL-1β, neutrophil elastase, bradykinin, and Tissue Factor.
Main Results:
- * Inflammasome and TLR activation leads to excessive, detrimental inflammation in B. pseudomallei lung infections.
- * Interleukin (IL)-1β and neutrophil proteases contribute to lung tissue damage.
- * Caspase-11 activation is implicated in sepsis and coagulopathy via Tissue Factor activation.
Conclusions:
- * Caspase-11 activation represents a key pathogenic mechanism in melioidosis, contributing to sepsis and coagulopathy.
- * Inhibitors targeting inflammasomes, IL-1β, neutrophil elastase, bradykinin, and Tissue Factor show promise for melioidosis treatment.
