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Host and pathogen hyaluronan signal through human siglec-9 to suppress neutrophil activation.

Secundino, Ismael ; Lizcano, Anel ; Roupé, Markus LU ; Wang, Xiaoxia ; Cole, Jason N ; Olson, Joshua ; Ali, S Raza ; Dahesh, Samira ; Amayreh, Lenah K and Henningham, Anna , et al. (2016) In Journal of Molecular Medicine 94. p.219-219
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Molecular Medicine
volume
94
pages
233 pages
publisher
Springer
external identifiers
  • pmid:26411873
  • scopus:84959083877
  • wos:000371029700009
  • pmid:26411873
ISSN
1432-1440
DOI
10.1007/s00109-015-1341-8
language
English
LU publication?
yes
id
8bfa8d0e-78fc-4783-ad84-192ae74a39c7 (old id 8034740)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26411873?dopt=Abstract
date added to LUP
2016-04-04 08:56:27
date last changed
2022-03-23 03:35:57
@article{8bfa8d0e-78fc-4783-ad84-192ae74a39c7,
  abstract     = {{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.}},
  author       = {{Secundino, Ismael and Lizcano, Anel and Roupé, Markus and Wang, Xiaoxia and Cole, Jason N and Olson, Joshua and Ali, S Raza and Dahesh, Samira and Amayreh, Lenah K and Henningham, Anna and Varki, Ajit and Nizet, Victor}},
  issn         = {{1432-1440}},
  language     = {{eng}},
  pages        = {{219--219}},
  publisher    = {{Springer}},
  series       = {{Journal of Molecular Medicine}},
  title        = {{Host and pathogen hyaluronan signal through human siglec-9 to suppress neutrophil activation.}},
  url          = {{http://dx.doi.org/10.1007/s00109-015-1341-8}},
  doi          = {{10.1007/s00109-015-1341-8}},
  volume       = {{94}},
  year         = {{2016}},
}