interleukin-8 and Fasciitis--Necrotizing

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.

Topics: Amino Acid Sequence; Animals; Bacterial Proteins; Cell Migration Inhibition; Electrophoresis, Polyacrylamide Gel; Fasciitis, Necrotizing; Female; Humans; Interleukin-8; Mice; Mice, Inbred C57BL; Models, Molecular; Molecular Sequence Data; Neutrophil Activation; Neutrophils; Peptide Hydrolases; Streptococcus pyogenes