Specific C-terminal cleavage and inactivation of interleukin-8 by invasive disease isolates of Streptococcus pyogenes.
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.
Edwards
Robert J
RJ
Section of Experimental Medicine and Toxicology, Faculty of Medicine, Imperial College London, London, United Kingdom.
Taylor
Graham W
GW
Ferguson
Melissa
M
Murray
Stephen
S
Rendell
Nigel
N
Wrigley
Amanda
A
Bai
Zhonghu
Z
Boyle
Joseph
J
Finney
Simon J
SJ
Jones
Angus
A
Russell
Hugh H
HH
Turner
Claire
C
Cohen
Jonathan
J
Faulkner
Lee
L
Sriskandan
Shiranee
S
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
D001426:Bacterial Proteins; D016209:Interleukin-8; D010447:Peptide Hydrolases; C527349:SpyCEP protein, Streptococcus pyogenes