Molecular mechanisms of cell death and inflammatory responses of antigen presenting cells upon infection of mucosal pathogenic bacteria
| Project/Area Number |
18390133
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
SUZUKI Toshihiko University of the Ryukyus, Graduate School of Medicine, Professor (10292848)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥16,400,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2007: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2006: ¥9,900,000 (Direct Cost: ¥9,900,000)
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| Keywords | Shigella / macrophages / cell death / inflammation |
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| Research Abstract |
Shigella are bacterial pathogens that are the cause of bacillary dysentery known as shigellosis. A crucial aspect of the propensity of Shigella to cause diseases lies in its ability to invade into the cytoplasm of epithelial cells as well as macrophages. The bacterial invasion into macrophages induces pyroptosis, the proinflammatory cell death associated with caspase-1 activation. Activated caspase-1 then cleaves and activates prointerleukin (IL)-1β and proIL-18 that are proinflammatory cytokines involved in host inflammatory responses. However, the precise mechanisms of caspase-1 activation induced by Shigella infection remain poorly understood. Ipaf, a cytosolic pattern-recognition receptor of the nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family is a crucial host factor to activate caspase-1 through the sensing of flagellin produced by some bacteria such as Salmonella or Legionella. The authors discovered that Ipaf and the adaptor protein ASC are required for caspase-1 activation induced by non-flagellated Shigella infection. Thus Ipaf and ASC mediate caspase-1 activation by sensing unknown bacterial factor but not flagellin. Autophagy, a cellular system for eliminating intracellular pathogens, was dramatically enhanced in Shigella-infected macrophages by the absence of caspase-1 or Ipaf, but not ASC. The inhibition of autophagy promoted Shigella-induced cell death, suggesting that autophagy protects infected macrophages from pyroptosis. This study provides evidence that in Shigella-infected macrophages, autophagy is inhibited by Ipaf and caspase-1, whereas positively regulated by ASC, providing a novel function for NLR proteins in bacterial-host interactions.
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Report
(3 results)
Research Products
(29 results)
