SpeB of Streptococcus Pyogenes Differentially Modulates Antibacterial and Receptor Activating Properties of Human Chemokines

PLoS One. 2009;4(3):e4769. doi: 10.1371/journal.pone.0004769. Epub 2009 Mar 10.

Abstract

Background: CXC chemokines are induced by inflammatory stimuli in epithelial cells and some, like MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11, are antibacterial for Streptococcus pyogenes.

Methodology/principal findings: SpeB from S. pyogenes degrades a wide range of chemokines (i.e. IP10/CXCL10, I-TAC/CXCL11, PF4/CXCL4, GROalpha/CXCL1, GRObeta/CXCL2, GROgamma/CXCL3, ENA78/CXCL5, GCP-2/CXCL6, NAP-2/CXCL7, SDF-1/CXCL12, BCA-1/CXCL13, BRAK/CXCL14, SRPSOX/CXCL16, MIP-3alpha/CCL20, Lymphotactin/XCL1, and Fractalkine/CX3CL1), has no activity on IL-8/CXCL8 and RANTES/CCL5, partly degrades SRPSOX/CXCL16 and MIP-3alpha/CCL20, and releases a 6 kDa CXCL9 fragment. CXCL10 and CXCL11 loose receptor activating and antibacterial activities, while the CXCL9 fragment does not activate the receptor CXCR3 but retains its antibacterial activity.

Conclusions/significance: SpeB destroys most of the signaling and antibacterial properties of chemokines expressed by an inflamed epithelium. The exception is CXCL9 that preserves its antibacterial activity after hydrolysis, emphasizing its role as a major antimicrobial on inflamed epithelium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / physiology*
  • Blood Bactericidal Activity
  • Chemokine CXCL10 / immunology
  • Chemokine CXCL11 / immunology
  • Chemokine CXCL9 / immunology
  • Chemokines / immunology*
  • Epithelium
  • Exotoxins / physiology*
  • Humans
  • Immunity, Innate*
  • Inflammation
  • Streptococcus pyogenes / pathogenicity*

Substances

  • Bacterial Proteins
  • CXCL10 protein, human
  • CXCL11 protein, human
  • CXCL9 protein, human
  • Chemokine CXCL10
  • Chemokine CXCL11
  • Chemokine CXCL9
  • Chemokines
  • Exotoxins
  • erythrogenic toxin