Specific C‐Terminal Cleavage and Inactivation of Interleukin‐8 by Invasive Disease Isolates ofStreptococcus pyogenes | Zendy

Robert J. Edwards | Zendy; Graham W. Taylor | Zendy; Melissa Ferguson | Zendy; Stephen A. Murray | Zendy; Nigel B. Rendell | Zendy; Amanda Wrigley | Zendy; Zhonghu Bai | Zendy; Joseph Boyle | Zendy; Simon J. Finney | Zendy; Angus G. Jones | Zendy; Hugh Russell | Zendy; Claire E. Turner | Zendy; Jonathan Cohen | Zendy; Lee Faulkner | Zendy; Shiranee Sriskandan | Zendy

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Specific C‐Terminal Cleavage and Inactivation of Interleukin‐8 by Invasive Disease Isolates ofStreptococcus pyogenes

Author(s) -

Robert J. Edwards,

Graham W. Taylor,

Melissa Ferguson,

Stephen A. Murray,

Nigel B. Rendell,

Amanda Wrigley,

Zhonghu Bai,

Joseph Boyle,

Simon J. Finney,

Angus G. Jones,

Hugh Russell,

Claire E. Turner,

Jonathan Cohen,

Lee Faulkner,

Shiranee Sriskandan

Publication year - 2005

Publication title -

the journal of infectious diseases

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.69

H-Index - 252

eISSN - 1537-6613

pISSN - 0022-1899

DOI - 10.1086/432485

Subject(s) - streptococcus pyogenes , microbiology and biotechnology , biology , cleavage (geology) , interleukin , chemistry , cytokine , bacteria , immunology , staphylococcus aureus , fracture (geology) , paleontology , genetics

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.

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