| Project/Area Number |
26860283
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Bacteriology (including mycology)
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| Research Institution | The University of Tokyo |
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Principal Investigator |
Suzuki Shiho 東京大学, 医科学研究所, 特任助教 (80444074)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | inflammasome / 赤痢菌 / NAIP / NLRC4 / インフラマソーム / Pyroptosis |
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| Outline of Final Research Achievements |
Shigella are bacterial pathogens that are the cause of bacillary dysentery. An important feature of Shigella is their ability to invade the cytoplasm of host epithelial cells and macrophages. A major component of host recognition of Shigella invasion is the activation of the inflammasome, a molecular platform that drives the activation of caspase-1 in macrophages. Although Shigella is known to induce the activation of the Nlrc4 inflammasome, the mechanism by which the bacterium activates Nlrc4 is largely unknown. We discovered that the Shigella T3SS inner rod protein MxiI induces Nlrc4 inflammasome activation through the interaction with host Naip2, which promoted the association of Naip2 with Nlrc4 in macrophages. Expression of MxiI induced caspase-1 activation, Asc oligomerization, pyroptosis and IL-1b release which required Naip2, but not Naip5.This study elucidates the microbial-host interactions that drive the activation of the Nlrc4 inflammasome in Shigella-infected macrophages.
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