Antibacterial peptides - key players in host defense at epithelial surfaces
(2010) In Lund University Faculty of Medicine Doctoral Dissertation Series 2010:7.- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1524502
- author
- Eliasson, Mette LU
- supervisor
-
- Arne Egesten LU
- Ole E Sørensen LU
- opponent
-
- Ass Prof Bylund, Johan, Inst of Medicine, Dep of Rheumatology and Inflammation research, University of Gothenburg
- organization
- publishing date
- 2010
- type
- Thesis
- publication status
- published
- subject
- keywords
- mucosa, epithelium, pharyngitis, Innate immunity, Streptococcus pyogenes, antibacterial peptides, IFN-gamma, CXCL9/MIG, chemokines
- in
- Lund University Faculty of Medicine Doctoral Dissertation Series
- volume
- 2010:7
- pages
- 124 pages
- publisher
- Lund University: Faculty of Medicine
- defense location
- Lundmarksalen, Astronomihuset , Lund University
- defense date
- 2010-01-29 09:15:00
- ISSN
- 1652-8220
- ISBN
- 978-91-86443-21-4
- language
- English
- LU publication?
- yes
- id
- f9125bf9-1027-4d66-8c9b-104b50e8eacd (old id 1524502)
- date added to LUP
- 2016-04-01 13:34:27
- date last changed
- 2019-11-19 13:49:05
@phdthesis{f9125bf9-1027-4d66-8c9b-104b50e8eacd, 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.}}, author = {{Eliasson, Mette}}, isbn = {{978-91-86443-21-4}}, issn = {{1652-8220}}, keywords = {{mucosa; epithelium; pharyngitis; Innate immunity; Streptococcus pyogenes; antibacterial peptides; IFN-gamma; CXCL9/MIG; chemokines}}, language = {{eng}}, publisher = {{Lund University: Faculty of Medicine}}, school = {{Lund University}}, series = {{Lund University Faculty of Medicine Doctoral Dissertation Series}}, title = {{Antibacterial peptides - key players in host defense at epithelial surfaces}}, url = {{https://lup.lub.lu.se/search/files/3453270/1524627.pdf}}, volume = {{2010:7}}, year = {{2010}}, }