The CXC chemokine MIG/CXCL9 is important in innate immunity against Streptococcus pyogenes

Arne Egesten1, Mette Eliasson, Helena M Johansson

  • 1Section for Respiratory Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. Arne.Egesten@med.lu.se

Insights

Streptococcus pyogenes pharyngitis involves high levels of monokine induced by interferon-gamma (MIG/CXCL9), an interferon-dependent chemokine. This chemokine and others exhibit antibacterial activity, revealing a new innate defense against invasive bacteria.

Area of Science:

  • Immunology
  • Microbiology
  • Infectious Diseases

Background:

  • Streptococcus pyogenes pharyngitis is a common infection and a precursor to invasive disease.
  • The role of epithelial-derived chemokines in combating S. pyogenes at mucosal surfaces is not fully understood.

Purpose of the Study:

  • To investigate the role of interferon-dependent CXC chemokines in the innate immune response to S. pyogenes pharyngitis.
  • To identify specific chemokines involved in antibacterial defense at the pharyngeal epithelium.

Main Methods:

  • Quantification of monokine induced by interferon-gamma (MIG/CXCL9) in tonsil fluid from patients with streptococcal pharyngitis.
  • In vitro assessment of MIG/CXCL9 production by inflamed pharyngeal epithelium upon bacterial exposure.
  • Evaluation of the antibacterial activity of CXC chemokines (MIG/CXCL9, CXCL10, CXCL11) against S. pyogenes.
  • Assessment of the impact of MIG/CXCL9 inhibition on antibacterial activity.
  • Analysis of the effect of Streptococcus pyogenes streptococcal inhibitor of complement (SIC) on chemokine activity.

Main Results:

  • Tonsil fluid from patients with S. pyogenes pharyngitis showed elevated levels of MIG/CXCL9.
  • Inflamed pharyngeal epithelial cells produced significant amounts of MIG/CXCL9 in the presence of S. pyogenes.
  • MIG/CXCL9, CXCL10, and CXCL11 demonstrated direct antibacterial activity against S. pyogenes.
  • Inhibiting MIG/CXCL9 reduced the antibacterial capacity of inflamed pharyngeal cells.
  • The S. pyogenes protein SIC neutralized the antibacterial effects of these chemokines.

Conclusions:

  • CXC chemokines, particularly MIG/CXCL9, represent a novel innate defense mechanism against S. pyogenes on epithelial surfaces.
  • S. pyogenes employs strategies, like SIC production, to evade this chemokine-mediated immunity.
  • Understanding this interaction is crucial for developing strategies against invasive S. pyogenes infections.

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