title: Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei.
abstract: 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.
authors.affiliation: Department of Biochemistry, National University of Singapore.
authors.forename: Guang Wen
authors.initials: GW
authors.lastname: Sun
authors.forename: Jinhua
authors.initials: J
authors.lastname: Lu
authors.forename: Shazib
authors.initials: S
authors.lastname: Pervaiz
authors.forename: Wei Ping
authors.initials: WP
authors.lastname: Cao
authors.forename: Yunn-Hwen
authors.initials: YH
authors.lastname: Gan
mesh_terms: 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
chemical_list: D007375:Interleukin-1; D020382:Interleukin-18; D020170:Caspase 1