title: Specific C-terminal cleavage and inactivation of interleukin-8 by invasive disease isolates of Streptococcus pyogenes.
abstract: Lethal necrotizing fasciitis caused by Streptococcus pyogenes is characterized by a paucity of neutrophils at the site of infection. Interleukin (IL)-8, which is important for neutrophil transmigration and activation, can be degraded by S. pyogenes. Blood isolates of S. pyogenes were better able to degrade human IL-8 than throat isolates. Degradation of IL-8 was the result of a single specific cleavage between 59glutamine and 60arginine within the IL-8 C-terminal alpha helix. Cleaved IL-8 reduced neutrophil activation and migration. IL-8-cleaving activity was found in partially purified supernatant of a necrotizing fasciitis isolate, and this activity was associated with an approximately 150-kDa fraction containing S. pyogenes cell envelope proteinase (SpyCEP). IL-8-cleaving activity corresponded with the presence of SpyCEP in the supernatant. Cleavage of IL-8 by S. pyogenes represents an unprecedented mechanism of immune evasion, effectively preventing IL-8 C-terminus-mediated endothelial translocation and subsequent recruitment of neutrophils.
authors.affiliation: Section of Experimental Medicine and Toxicology, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Edwards
authors.forename: Graham W
authors.initials: GW
authors.lastname: Taylor
authors.forename: Melissa
authors.initials: M
authors.lastname: Ferguson
authors.forename: Stephen
authors.initials: S
authors.lastname: Murray
authors.forename: Nigel
authors.initials: N
authors.lastname: Rendell
authors.forename: Amanda
authors.initials: A
authors.lastname: Wrigley
authors.forename: Zhonghu
authors.initials: Z
authors.lastname: Bai
authors.forename: Joseph
authors.initials: J
authors.lastname: Boyle
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Finney
authors.forename: Angus
authors.initials: A
authors.lastname: Jones
authors.forename: Hugh H
authors.initials: HH
authors.lastname: Russell
authors.forename: Claire
authors.initials: C
authors.lastname: Turner
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
authors.forename: Lee
authors.initials: L
authors.lastname: Faulkner
authors.forename: Shiranee
authors.initials: S
authors.lastname: Sriskandan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D002464:Cell Migration Inhibition; D004591:Electrophoresis, Polyacrylamide Gel; D019115:Fasciitis, Necrotizing / Q000276:immunology / Q000382:microbiology*; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018375:Neutrophil Activation / Q000276:immunology*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D010447:Peptide Hydrolases / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000166:cytology / Q000201:enzymology* / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D016209:Interleukin-8; D010447:Peptide Hydrolases; C527349:SpyCEP protein, Streptococcus pyogenes