Heparan Sulfate Modulates Neutrophil and Endothelial Function in Antibacterial Innate Immunity
Journal
Infection and immunity
Journal Volume
83
Journal Issue
9
Pages
3648
Date Issued
2015-09
Author(s)
Xu, Ding
Olson, Joshua
Cole, Jason N
van Wijk, Xander M
Brinkmann, Volker
Zychlinsky, Arturo
Nizet, Victor
Esko, Jeffrey D
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.
SDGs
Other Subjects
heparan sulfate; heparan sulfate uronyl 2 o sulfotransferase; histone; I kappa B; interleukin 1beta; interleukin 6; messenger RNA; monocyte chemotactic protein 1; polypeptide antibiotic agent; reactive oxygen metabolite; stress activated protein kinase; unclassified drug; heparan-sulfate 2-sulfotransferase; proteoheparan sulfate; sulfotransferase; animal cell; animal experiment; animal model; animal tissue; apoptosis; Article; bacterial growth; bacterial survival; bacterial virulence; bactericidal activity; bacterium; bacterium adherence; capillary endothelial cell; cell function; cell stimulation; cell structure; colony forming unit; controlled study; cytokine release; cytokine response; endothelium cell; enzyme inactivation; enzyme localization; enzyme phosphorylation; extracellular trap; gene deletion; group B streptococcal infection; human; human cell; in vivo study; infection resistance; infection sensitivity; inflammation; innate immunity; mouse; nerve cell lesion; neutrophil chemotaxis; nonhuman; phagocytosis; priority journal; protein blood level; protein degradation; protein expression; sulfation; animal; cell culture; disease model; endothelium cell; immunology; innate immunity; metabolism; neutrophil; scanning electron microscopy; Streptococcus agalactiae; Streptococcus infection; Western blotting; Animals; Blotting, Western; Cells, Cultured; Disease Models, Animal; Endothelial Cells; Extracellular Traps; Heparan Sulfate Proteoglycans; Immunity, Innate; Mice; Microscopy, Electron, Scanning; Neutrophils; Streptococcal Infections; Streptococcus agalactiae; Sulfotransferases
Publisher
AMER SOC MICROBIOLOGY
Type
journal article