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Assessment of Lymphocyte Migration in an Ex Vivo Transmigration System
Published on: September 20, 2019
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
Abstract:
Pharyngitis caused by Streptococcus pyogenes is one of the most common bacterial infections in humans and is also a starting point for invasive S. pyogenes infection. Here, we describe that tonsil fluid from patients with streptococcal pharyngitis contains high amounts of the interferon (IFN)-dependent CXC chemokine known as monokine induced by IFN- gamma (MIG)/CXCL9. Also in vitro, inflamed pharyngeal epithelium produced large amounts of MIG/CXCL9 in the presence of bacteria. The CXC chemokines MIG/CXCL9, IFN-inducible protein-10/CXCL10, and IFN-inducible T cell alpha -chemoattractant/CXCL11 all showed antibacterial activity against S. pyogenes, and inhibition of MIG/CXCL9 expression reduced the antibacterial activity at the surface of inflamed pharyngeal cells. S. pyogenes of the clinically important M1 serotype secrets the protein streptococcal inhibitor of complement (SIC), which inhibited the antibacterial activity of the chemokines. As exemplified by S. pyogenes pharyngitis, the data identify a novel innate defense mechanism against invasive bacteria on epithelial surfaces.
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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Streptococcal Pharyngitis

