Antibacterial peptides - key players in host defense at epithelial surfaces

Mette Eliasson

Research output: ThesisDoctoral Thesis (compilation)

151 Downloads (Pure)

Abstract

Innate host defense mechanisms at epithelial surfaces are important to prevent bacterial invasion. Streptococcus pyogenes, group A streptococcus (GAS), has an affinity for epithelial cells and cause pharyngitis. During streptococcal pharyngitis, high concentrations of the chemokines CXCL9/MIG, CXCL10/IP-10, CXCL11/I-TAC were found in tonsil fluid. Similarly, these chemokines were produced by activated pharyngeal epithelial cells in vitro. CXCL9/MIG was the predominant chemokine and also the most potent in killing GAS. Epithelial recognition of GAS, or its important virulence factor protein M1, was demonstrated by an increased production of CXCL9/MIG. Stimulation with proinflammatory cytokines induced a high antibacterial activity against GAS, both in the incubation medium and retained on the cell surface. Knockdown of CXCL9/MIG-production resulted in a decreased antibacterial activity. The soluble antibacterial activity was dependent on IFN-γ and mediated by a variety of antibacterial chemokines and antibacterial peptides. SIC, a released protein of GAS inhibited the antibacterial effect of both CXCL9/MIG, and of incubation medium from stimulated cells. The virulent GAS, but not the commensal Finegoldia magna, induced an immune response in keratinocytes, as exemplified by an increase in CXCL9/MIG-expression. The F. magna protease SufA degraded CXCL9/MIG into fragments not bactericidal to the bacterium itself, but to GAS. Additionally, F. magna adhesion factor, FAF, inhibited the antibacterial effect of CXCL9/MIG. Taken together, the epithelium recognizes pathogens, but not commensals, and a bactericidal response is initiated. The response is dependent on IFN-γ, and mediated by antibacterial peptides, where the IFN-γ- inducible antibacterial chemokine CXCL9/MIG is important.
Original languageEnglish
QualificationDoctor
Awarding Institution
  • Respiratory Medicine, Allergology, and Palliative Medicine
Supervisors/Advisors
  • Egesten, Arne, Supervisor
  • Sörensen, Ole, Supervisor
Award date2010 Jan 29
Publisher
ISBN (Print)978-91-86443-21-4
Publication statusPublished - 2010

Bibliographical note

Defence details

Date: 2010-01-29
Time: 09:15
Place: Lundmarksalen, Astronomihuset , Lund University

External reviewer(s)

Name: Bylund, Johan
Title: Ass Prof
Affiliation: Inst of Medicine, Dep of Rheumatology and Inflammation research, University of Gothenburg

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Subject classification (UKÄ)

  • Respiratory Medicine and Allergy
  • Other Clinical Medicine

Free keywords

  • mucosa
  • epithelium
  • pharyngitis
  • Innate immunity
  • Streptococcus pyogenes
  • antibacterial peptides
  • IFN-gamma
  • CXCL9/MIG
  • chemokines

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