Host and pathogen hyaluronan signal through human siglec-9 to suppress neutrophil activation.
J Mol Med (Berl)
; 94(2): 219-33, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26411873
ABSTRACT
UNLABELLED Inhibitory CD33-related Siglec receptors regulate immune cell activation upon engaging ubiquitous sialic acids (Sias) on host cell surface glycans. Through molecular mimicry, Sia-expressing pathogen group B Streptococcus binds inhibitory human Siglec-9 (hSiglec-9) to blunt neutrophil activation and promote bacterial survival. We unexpectedly discovered that hSiglec-9 also specifically binds high molecular weight hyaluronan (HMW-HA), another ubiquitous host glycan, through a region of its terminal Ig-like V-set domain distinct from the Sia-binding site. HMW-HA recognition by hSiglec-9 limited neutrophil extracellular trap (NET) formation, oxidative burst, and apoptosis, defining HMW-HA as a regulator of neutrophil activation. However, the pathogen group A Streptococcus (GAS) expresses a HMW-HA capsule that engages hSiglec-9, blocking NET formation and oxidative burst, thereby promoting bacterial survival. Thus, a single inhibitory lectin receptor detects two distinct glycan "self-associated molecular patterns" to maintain neutrophil homeostasis, and two leading human bacterial pathogens have independently evolved molecular mimicry to exploit this immunoregulatory mechanism. KEY MESSAGE HMW-HA is the first example of a non-sialic acid containing glycan to be recognized by CD33-related Siglecs. HMW-HA engagement of hSiglec-9 attenuates neutrophil activation. Group A Streptococcus exploits hSiglec-9 recognition via its polysaccharide HMW-HA capsule to subvert neutrophil killing.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Antígenos CD
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Ativação de Neutrófilo
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Interações Hospedeiro-Patógeno
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Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico
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Ácido Hialurônico
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Neutrófilos
Limite:
Animals
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Humans
Idioma:
En
Revista:
J Mol Med (Berl)
Assunto da revista:
BIOLOGIA MOLECULAR
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GENETICA MEDICA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos