Role of the inflammasome in bacterial infections
| Project/Area Number |
23590504
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Bacteriology (including Mycology)
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| Research Institution | Kyoto University |
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Principal Investigator |
TSUCHIYA Kohsuke 京都大学, 医学(系)研究科(研究院), 助教 (50437216)
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | インフラマソーム / ASC / NLRP3 / 細菌感染 / リステリア / 肺炎球菌 / 感染防御 / AIM2 / I型インターフェロン / 肺粘膜 / 粘膜免疫 / Listeria monocytogenes / IL-18 / IL-10 / absent in melanoma 2 / カスパーゼ1 / 自然免疫 |
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| Outline of Final Research Achievements |
Inflammasomes are innate immune mechanisms that activate caspase-1 in response to various stimuli, including microbial pathogens. Once activated, inflammasomes induce the production of pro-inflammatory cytokines and programmed cell death through caspase-1. Accumulating data have suggested inflammasomes play a protective role against microbial infections. In this study, we examined the mechanism and role of inflammasome formation in infection with two Gram-positive bacteria. We found that Streptococcus pneumoniae is recognized by the cytosolic DNA receptor AIM2, which in turn forms an inflammasome complex to activate caspase-1. It was also found that inflammasomes are critical for host defense against pneumococcal pneumonia. On the other hand, inflammasomes were detrimental to the host in lethal infection with Listeria monocytogenes. Our study revealed that inflammasomes can be upstream of an immunosuppressive response, which may explain the detrimental effect of inflammasomes.
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Report
(5 results)
Research Products
(25 results)
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[Journal Article] The adaptor ASC exacerbates lethal Listeria monocytogenes infection by mediating IL-18 production in an inflammasome-dependent and -independent manner.2014
Author(s)
Tsuchiya K, Hara H, Fang R, Hernandez-Cuellar E, Sakai S, Daim S, Chen X, Dewamitta SR, Qu H, Mitsuyama M, Kawamura I.
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Journal Title
European Journal of Immunology
Volume: 44
Issue: 12
Pages: 3696-3707
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] The RD1 locus in the Mycobacterium tuberculosis genome contributes to the maturation and secretion of IL-1α from infected macrophages through the elevation of cytoplasmic calcium levels and calpain activation.2014
Author(s)
Yang R, Xi C, Sita DR, Sakai S, Tsuchiya K, Hara H, Shen Y, Qu H, Fang R, Mitsuyama M, Kawamura I.
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Journal Title
Pathog Dis.
Volume: 70
Issue: 1
Pages: 51-60
DOI
Related Report
Peer Reviewed
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[Journal Article] Critical roles of ASC in flammasomes in caspase-1 activation and host innate resistance to Streptococcus pneumoniae infection.2011
Author(s)
R. Fang, K. Tsuchiya, I. Kawamura, Y. Shen, H. Hara, S. Sakai, T. Yamamoto, T. Fernandes-Alnemri, R. Yang, E. Hernandez-Cuellar, S. R. Dewamitta, Y. Xu, H. Qu, E. S. Alnemri, and M. Mitsuyama
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Journal Title
J. Immunol
Volume: 187
Issue: 9
Pages: 4890-4899
DOI
Related Report
Peer Reviewed
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