Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection.
Proc Natl Acad Sci U S A
; 115(45): E10662-E10671, 2018 11 06.
Article
em En
| MEDLINE
| ID: mdl-30352847
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.
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MEDLINE
Assunto principal:
Infecções Estreptocócicas
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Streptococcus pyogenes
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Ácidos Teicoicos
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Lipopolissacarídeos
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Lectinas Tipo C
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Proteínas de Membrana
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article