Caspase-1 dependent macrophage death induced by Burkholderia pseudomallei

Abstract

SummaryBurkholderia pseudomallei is the causative agent for melioidosis, an infectious disease endemic in Southeast 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-1 b b b b 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.

Pseudomonas aeruginosa activates caspase 1 through Ipaf

“…Other Gram-negative pathogens activate caspase 1 through the activity of T3SS, including Burkholderia pseudomallei (35), which also expresses flagellin. Moreover, it is known that L. pneumophila flagellin also activates Ipaf.…”

Type III secretion system 1 of Vibrio parahaemolyticus induces oncosis in both epithelial and monocytic cell lines

“…These findings are consistent with cell death induced by oncosis; this phenotype was abrogated by addition of PEG3350, but not by osmoprotectants with a molecular diameter less than that of PEG3350, suggesting that the pore sizes on the host membrane are between 2.4 and 3.8 nm. This is larger than pores that are created by Pseudomonas (1.3-2.8 nm), Salmonella (1.1-2.4 nm) and Burkholderia (1.4-2.4 nm) (Dacheux et al, 2001;Fink & Cookson, 2006;Sun et al, 2005).…”

“…These structures become inserted into the cell membrane to create pores in the membrane surface (Neyt & Cornelis, 1999); these pores assist the translocation of effector proteins from bacteria into host cells (Neyt & Cornelis, 1999). In some cases, pore formation results in the entry of small ions and water from the extracellular milieu into the cytosol of host cells leading to cellular oncotic lysis (Dacheux et al, 2001;Fink & Cookson, 2006;Sun et al, 2005). For example, T3SSs of Pseudomonas, Salmonella and Burkholderia induce oncosis of macrophages that can be prevented by addition of osmoprotectants such as PEG with a molecular diameter larger than that of the pores.…”

Cell death in the host response to infection

“…82,83 In contrast, the inhibitor of actin rearrangement, cytochalasin D, interferes with bacterial entry into the cytosol and caspase-1 activation. 41,49,52,56,66 In some cases, the effector molecule responsible for caspase-1 activation has been identified. For the flagellated bacteria Salmonella typhimurium, 82,83 Legionella pneumophila, 54 and Pseudomonas aeruginosa, 86,91 proper expression of flagellin is required for caspase-1 activation.…”