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PMID:27068089
| Citation |
Arizmendi, O, Picking, WD and Picking, WL (2016) Macrophage Apoptosis Triggered by IpaD from Shigella flexneri. Infect. Immun. 84:1857-65 |
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| Abstract |
Shigellosis, a potentially severe bacillary dysentery, is an infectious gastrointestinal disease caused by Shigella spp. Shigella invades the human colonic epithelium and avoids clearance by promoting apoptosis of resident immune cells in the gut. This process is dependent on the Shigella type III secretion system (T3SS), which injects effector proteins into target cells to alter their normal cellular functions. Invasion plasmid antigen D (IpaD) is a structural component that forms a complex at the tip of the T3SS apparatus needle. Recently, IpaD has also been shown to indirectly induce apoptosis in B lymphocytes. In this study, we explored the cytotoxicity profile during macrophage infection by Shigella and discovered that the pathogen induces macrophage cell death independent of caspase-1. Our results demonstrate that IpaD triggers apoptosis in macrophages through activation of host caspases accompanied by mitochondrial disruption. Additionally, we found that the IpaD N-terminal domain is necessary for macrophage killing and SipD, a structural homologue from Salmonella, was found to promote similar cytotoxicity. Together, these findings indicate that IpaD is a contributing factor to macrophage cell death during Shigella infection. |
| Links |
PubMed PMC4907132 Online version:10.1128/IAI.01483-15 |
| Keywords |
Animals; Antigens, Bacterial/genetics; Antigens, Bacterial/metabolism; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Caspases/genetics; Caspases/metabolism; Cell Death; Cell Line; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Macrophages/microbiology; Macrophages/pathology; Mice; Mitochondria/microbiology; Mitochondria/pathology; Protein Domains; Shigella flexneri/genetics; Shigella flexneri/metabolism; Shigella flexneri/pathogenicity; Signal Transduction; Type III Secretion Systems/genetics; Type III Secretion Systems/metabolism |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0034055: positive regulation by symbiont of host defense-related programmed cell death |
ECO:0000314: |
P |
Organism: Shigella Flexneri The protein is called IpaD. Figure 4A shows that macrophages(part of the host immune system) exposed to the S. flexneri ipaD protein died. Figure 5B shows that ipaD promotes caspace activity, which is part of the apoptotic pathway in cells and part of the defense mechanism of the host, meaning that ipaD upregulated programmed cell death mechanisms in its host. |
complete | ||||
Notes
See also
References
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