Targeting inflammasome, IL-1β, and coagulation in melioidosis

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.