Heparan sulfate modulates neutrophil and endothelial function in antibacterial innate immunity

Xu, Ding, Olson, Joshua, Cole, Jason N, van Wijk, Xander M, Brinkmann, Volker, Zychlinsky, Arturo, Nizet, Victor, Esko, Jeffrey D and Chang, Yung-Chi (2015) Heparan sulfate modulates neutrophil and endothelial function in antibacterial innate immunity. Infection and Immunity, 83 9: 3648-3656. doi:10.1128/IAI.00545-15

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Author Xu, Ding
Olson, Joshua
Cole, Jason N
van Wijk, Xander M
Brinkmann, Volker
Zychlinsky, Arturo
Nizet, Victor
Esko, Jeffrey D
Chang, Yung-Chi
Title Heparan sulfate modulates neutrophil and endothelial function in antibacterial innate immunity
Journal name Infection and Immunity   Check publisher's open access policy
ISSN 1098-5522
Publication date 2015-09
Year available 2015
Sub-type Article (original research)
DOI 10.1128/IAI.00545-15
Open Access Status File (Publisher version)
Volume 83
Issue 9
Start page 3648
End page 3656
Total pages 9
Place of publication Washington, United States
Publisher American Society for Microbiology
Collection year 2016
Language eng
Formatted abstract
Recently, we showed that endothelial heparan sulfate facilitates entry of a bacterial pathogen into the central nervous system. Here, we show that normal bactericidal activity of neutrophils is influenced by the sulfation pattern of heparan sulfate. Inactivation of heparan sulfate uronyl 2-O-sulfotransferase (Hs2st) in neutrophils substantially reduced their bactericidal activity, and Hs2st deficiency rendered mice more susceptible to systemic infection with the pathogenic bacterium group B Streptococcus. Specifically, altered sulfation of heparan sulfate in mutant neutrophils affected formation of neutrophil extracellular traps while not influencing phagocytosis, production of reactive oxygen species, or secretion of granular proteases. Heparan sulfate proteoglycan(s) is present in neutrophil extracellular traps, modulates histone affinity, and modulates their microbial activity. Hs2st-deficient brain endothelial cells show enhanced binding to group B Streptococcus and are more susceptible to apoptosis, likely contributing to the observed increase in dissemination of group B Streptococcus into the brain of Hs2st-deficient mice following intravenous challenge. Taken together, our data provide strong evidence that heparan sulfate from both neutrophils and the endothelium plays important roles in modulating innate immunity.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 1 times in Thomson Reuters Web of Science Article | Citations
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