Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection

Takashi Imai, Takayuki Matsumura, Sabine Mayer-Lambertz, Christine A. Wells, Eri Ishikawa, Suzanne K. Butcher, Timothy C. Barnett, Mark J. Walker, Akihiro Imamura, Hideharu Ishida, Tadayoshi Ikebe, Tomofumi Miyamoto, Manabu Ato, Shoichi Ohga, Bernd Lepenies, Nina M. Van Sorge, Sho Yamasaki

研究成果: ジャーナルへの寄稿記事

7 引用 (Scopus)

抄録

Group A Streptococcus (GAS) is a Gram-positive bacterial pathogen that causes a range of diseases, including fatal invasive infections. However, the mechanisms by which the innate immune system recognizes GAS are not well understood. We herein report that the C-type lectin receptor macrophage inducible C-type lectin (Mincle) recognizes GAS and initiates antibacterial immunity. Gene expression analysis of myeloid cells upon GAS stimulation revealed the contribution of the caspase recruitment domain-containing protein 9 (CARD9) pathway to the antibacterial responses. Among receptors signaling through CARD9, Mincle induced the production of inflammatory cytokines, inducible nitric oxide synthase, and reactive oxygen species upon recognition of the anchor of lipoteichoic acid, monoglucosyldiacylglycerol (MGDG), produced by GAS. Upon GAS infection, Mincle-deficient mice exhibited impaired production of proinflammatory cytokines, severe bacteremia, and rapid lethality. GAS also possesses another Mincle ligand, diglucosyldiacylglycerol; however, this glycolipid interfered with MGDG-induced activation. These results indicate that Mincle plays a central role in protective immunity against acute GAS infection.

元の言語英語
ページ(範囲)E10662-E10671
ジャーナルProceedings of the National Academy of Sciences of the United States of America
115
発行部数45
DOI
出版物ステータス出版済み - 11 6 2018

Fingerprint

C-Type Lectins
Streptococcus
Immunity
Macrophages
Infection
Cytokines
lipoteichoic acid
Glycolipids
Nitric Oxide Synthase Type II
Myeloid Cells
Bacteremia
Immune System
Reactive Oxygen Species
Proteins
Ligands
Gene Expression

All Science Journal Classification (ASJC) codes

  • General

これを引用

Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection. / Imai, Takashi; Matsumura, Takayuki; Mayer-Lambertz, Sabine; Wells, Christine A.; Ishikawa, Eri; Butcher, Suzanne K.; Barnett, Timothy C.; Walker, Mark J.; Imamura, Akihiro; Ishida, Hideharu; Ikebe, Tadayoshi; Miyamoto, Tomofumi; Ato, Manabu; Ohga, Shoichi; Lepenies, Bernd; Van Sorge, Nina M.; Yamasaki, Sho.

:: Proceedings of the National Academy of Sciences of the United States of America, 巻 115, 番号 45, 06.11.2018, p. E10662-E10671.

研究成果: ジャーナルへの寄稿記事

Imai, T, Matsumura, T, Mayer-Lambertz, S, Wells, CA, Ishikawa, E, Butcher, SK, Barnett, TC, Walker, MJ, Imamura, A, Ishida, H, Ikebe, T, Miyamoto, T, Ato, M, Ohga, S, Lepenies, B, Van Sorge, NM & Yamasaki, S 2018, 'Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection', Proceedings of the National Academy of Sciences of the United States of America, 巻. 115, 番号 45, pp. E10662-E10671. https://doi.org/10.1073/pnas.1809100115
Imai, Takashi ; Matsumura, Takayuki ; Mayer-Lambertz, Sabine ; Wells, Christine A. ; Ishikawa, Eri ; Butcher, Suzanne K. ; Barnett, Timothy C. ; Walker, Mark J. ; Imamura, Akihiro ; Ishida, Hideharu ; Ikebe, Tadayoshi ; Miyamoto, Tomofumi ; Ato, Manabu ; Ohga, Shoichi ; Lepenies, Bernd ; Van Sorge, Nina M. ; Yamasaki, Sho. / Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection. :: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; 巻 115, 番号 45. pp. E10662-E10671.
@article{1d9822cc96344bbf9cf33e44e13bed75,
title = "Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection",
abstract = "Group A Streptococcus (GAS) is a Gram-positive bacterial pathogen that causes a range of diseases, including fatal invasive infections. However, the mechanisms by which the innate immune system recognizes GAS are not well understood. We herein report that the C-type lectin receptor macrophage inducible C-type lectin (Mincle) recognizes GAS and initiates antibacterial immunity. Gene expression analysis of myeloid cells upon GAS stimulation revealed the contribution of the caspase recruitment domain-containing protein 9 (CARD9) pathway to the antibacterial responses. Among receptors signaling through CARD9, Mincle induced the production of inflammatory cytokines, inducible nitric oxide synthase, and reactive oxygen species upon recognition of the anchor of lipoteichoic acid, monoglucosyldiacylglycerol (MGDG), produced by GAS. Upon GAS infection, Mincle-deficient mice exhibited impaired production of proinflammatory cytokines, severe bacteremia, and rapid lethality. GAS also possesses another Mincle ligand, diglucosyldiacylglycerol; however, this glycolipid interfered with MGDG-induced activation. These results indicate that Mincle plays a central role in protective immunity against acute GAS infection.",
author = "Takashi Imai and Takayuki Matsumura and Sabine Mayer-Lambertz and Wells, {Christine A.} and Eri Ishikawa and Butcher, {Suzanne K.} and Barnett, {Timothy C.} and Walker, {Mark J.} and Akihiro Imamura and Hideharu Ishida and Tadayoshi Ikebe and Tomofumi Miyamoto and Manabu Ato and Shoichi Ohga and Bernd Lepenies and {Van Sorge}, {Nina M.} and Sho Yamasaki",
year = "2018",
month = "11",
day = "6",
doi = "10.1073/pnas.1809100115",
language = "English",
volume = "115",
pages = "E10662--E10671",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "45",

}

TY - JOUR

T1 - Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection

AU - Imai, Takashi

AU - Matsumura, Takayuki

AU - Mayer-Lambertz, Sabine

AU - Wells, Christine A.

AU - Ishikawa, Eri

AU - Butcher, Suzanne K.

AU - Barnett, Timothy C.

AU - Walker, Mark J.

AU - Imamura, Akihiro

AU - Ishida, Hideharu

AU - Ikebe, Tadayoshi

AU - Miyamoto, Tomofumi

AU - Ato, Manabu

AU - Ohga, Shoichi

AU - Lepenies, Bernd

AU - Van Sorge, Nina M.

AU - Yamasaki, Sho

PY - 2018/11/6

Y1 - 2018/11/6

N2 - Group A Streptococcus (GAS) is a Gram-positive bacterial pathogen that causes a range of diseases, including fatal invasive infections. However, the mechanisms by which the innate immune system recognizes GAS are not well understood. We herein report that the C-type lectin receptor macrophage inducible C-type lectin (Mincle) recognizes GAS and initiates antibacterial immunity. Gene expression analysis of myeloid cells upon GAS stimulation revealed the contribution of the caspase recruitment domain-containing protein 9 (CARD9) pathway to the antibacterial responses. Among receptors signaling through CARD9, Mincle induced the production of inflammatory cytokines, inducible nitric oxide synthase, and reactive oxygen species upon recognition of the anchor of lipoteichoic acid, monoglucosyldiacylglycerol (MGDG), produced by GAS. Upon GAS infection, Mincle-deficient mice exhibited impaired production of proinflammatory cytokines, severe bacteremia, and rapid lethality. GAS also possesses another Mincle ligand, diglucosyldiacylglycerol; however, this glycolipid interfered with MGDG-induced activation. These results indicate that Mincle plays a central role in protective immunity against acute GAS infection.

AB - Group A Streptococcus (GAS) is a Gram-positive bacterial pathogen that causes a range of diseases, including fatal invasive infections. However, the mechanisms by which the innate immune system recognizes GAS are not well understood. We herein report that the C-type lectin receptor macrophage inducible C-type lectin (Mincle) recognizes GAS and initiates antibacterial immunity. Gene expression analysis of myeloid cells upon GAS stimulation revealed the contribution of the caspase recruitment domain-containing protein 9 (CARD9) pathway to the antibacterial responses. Among receptors signaling through CARD9, Mincle induced the production of inflammatory cytokines, inducible nitric oxide synthase, and reactive oxygen species upon recognition of the anchor of lipoteichoic acid, monoglucosyldiacylglycerol (MGDG), produced by GAS. Upon GAS infection, Mincle-deficient mice exhibited impaired production of proinflammatory cytokines, severe bacteremia, and rapid lethality. GAS also possesses another Mincle ligand, diglucosyldiacylglycerol; however, this glycolipid interfered with MGDG-induced activation. These results indicate that Mincle plays a central role in protective immunity against acute GAS infection.

UR - http://www.scopus.com/inward/record.url?scp=85056076405&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056076405&partnerID=8YFLogxK

U2 - 10.1073/pnas.1809100115

DO - 10.1073/pnas.1809100115

M3 - Article

VL - 115

SP - E10662-E10671

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 45

ER -