Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei.
Burkholderia pseudomallei is the causative agent for melioidosis, an infectious disease endemic in South-east Asia and northern Australia. Infection can result in a wide spectrum of clinical outcomes, including asymtomatic, acute or chronic conditions. The ability of the bacteria to survive intracellularly within phagocytes and non-phagocytes is postulated to help this pathogen persist in the body during latent chronic conditions. In some Gram-negative bacteria, such as Shigella and Salmonella, the ability to evade macrophage killing involves inducing rapid macrophage cell death. In several of these instances, these bacteria activate cellular caspase-1 to induce cell death, which is increasingly described to exhibit features more characteristic of oncosis than classical apoptosis. We found that B. pseudomallei is also capable of inducing caspase-1 dependent death in macrophages and this process requires a functional bsa Type III Secretion System (TTSS). Bacterial internalization and pore formation in the cell membrane is necessary for death. Furthermore, cell death is accompanied by the release of IL-1beta and IL-18. We believe that this novel description of macrophage death induced by B. pseudomallei could shed light on the pathogenesis of the bacteria in disease.
Sun
Guang Wen
GW
Department of Biochemistry, National University of Singapore.
Lu
Jinhua
J
Pervaiz
Shazib
S
Cao
Wei Ping
WP
Gan
Yunn-Hwen
YH
D000328:Adult; D000818:Animals; D016957:Burkholderia pseudomallei / Q000472:pathogenicity*; D020170:Caspase 1 / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000382:microbiology; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology*; D051379:Mice; D009000:Monocytes / Q000382:microbiology
D007375:Interleukin-1; D020382:Interleukin-18; D020170:Caspase 1