Functional analysis of immature myeloid cells in severe invasive group A streptococcal infection
Project/Area Number |
16K09952
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Infectious disease medicine
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Research Institution | National Institute of Infectious Diseases |
Principal Investigator |
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Keywords | 免疫学 / 細菌感染症 / 感染症防御学 / 劇症型溶血性レンサ球菌感染症 |
Outline of Final Research Achievements |
Severe invasive group A Streptococcus (GAS) infection evades anti-bacterial immunity by attenuating the cellular components of innate immune responses. However, this loss of protection is compensated for by IFN-γ-producing immature myeloid cells (γIMCs). Here, we demonstrate that γIMCs provide this IFN-γ-mediated protection by sequentially sensing GAS through two distinct pattern recognition receptors. GAS is initially recognized by TLR2, which promptly induces IL-6 production in γIMCs. γIMC-derived IL-6 promotes the upregulation of a recently identified GAS-sensing receptor, macrophage-inducible C-type lectin (Mincle), in an autocrine or paracrine manner. Notably, blockade of γIMC-derived IL-6 abrogates Mincle expression, downstream IFN-γ production, and γIMC-mediated protection against severe invasive GAS infection. Thus, γIMCs regulate host protective immunity against severe invasive GAS infection via a TLR2-IL-6-Mincle axis.
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Academic Significance and Societal Importance of the Research Achievements |
劇症型溶血性レンサ球菌感染症は約30%が死亡する致死率の高い感染症であり、メディア等では「人食いバクテリア」と称されている。国内年間報告数は、1999~2010年では多くても100例前後で推移、2011~2013年では200例前後を推移していたが、2014年に260例を超えてから増加の一途をたどり、2018年では680例を超えた。したがって既存の抗生物質による治療に追加可能な新規治療法の開発が必要であると考えられる。本研究の成果は、劇症型感染マウスモデルにおいて、新規細胞による連続的なレンサ球菌の認識機構が感染をコントロールできる可能性を見出している。
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Report
(4 results)
Research Products
(13 results)
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[Journal Article] Streptococcal toxic shock syndrome caused by β-hemolytic streptococci: clinical features and cytokine and chemokine analyses of 15 cases.2019
Author(s)
Yoshizawa S, Matsumura T, Ikebe T, Ichibayashi R, Fukui Y, Satoh T, Tsubota T, Honda M, Ishii Y, Tateda K, Ato M.
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Journal Title
J Infect Chemother
Volume: 25
Issue: 5
Pages: 355-361
DOI
Related Report
Peer Reviewed
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[Journal Article] Spontaneous mutations in Streptococcus pyogenes isolates from streptococcal toxic shock syndrome patients play roles in virulence.2016
Author(s)
1.Ikebe T, Matsumura T, Nihonmatsu H, Ohya H, Okuno R, Mitsui C, Kawahara R, Kameyama M, Sasaki M, Shimada N, Ato M, Ohnishi M.
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Journal Title
Scientific Reports
Volume: 6
Issue: 1
Pages: 28761-28761
DOI
Related Report
Peer Reviewed / Open Access
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