Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Interactions between Streptococcus pyogenes and the human immune defence

Nilsson, Maria E LU (2005)
Abstract
Streptococcus pyogenes is an important human pathogen frequently colonizing the throat and skin of humans. To facilitate colonization and spread and to avoid the host immune defence, streptococci are endowed with a variety of virulence factors, two of which are investigated in this thesis namely streptolysin O (SLO) and M protein.



SLO is a secreted cytolysin that forms pores in eukaryotic membranes by binding to cholesterol. This thesis shows that SLO, via calcium and p38 MAPK, stimulates polymorphonuclear neutrophilic granulocytes (PMNs) to release the pro-inflammatory mediators heparin binding protein (HBP), LL-37, ?-defensin, and elastase. This will lead to an exaggerated immune response that may be beneficial to... (More)
Streptococcus pyogenes is an important human pathogen frequently colonizing the throat and skin of humans. To facilitate colonization and spread and to avoid the host immune defence, streptococci are endowed with a variety of virulence factors, two of which are investigated in this thesis namely streptolysin O (SLO) and M protein.



SLO is a secreted cytolysin that forms pores in eukaryotic membranes by binding to cholesterol. This thesis shows that SLO, via calcium and p38 MAPK, stimulates polymorphonuclear neutrophilic granulocytes (PMNs) to release the pro-inflammatory mediators heparin binding protein (HBP), LL-37, ?-defensin, and elastase. This will lead to an exaggerated immune response that may be beneficial to streptococci and could explain some of the symptoms of severe streptococcal infections.



M proteins form a family of membrane anchored surface proteins that project from the streptococcal surface and have been linked to the characteristic feature of S. pyogenes to escape phagocytosis. The exact mechanisms underlying this phagocytosis resistance remain unknown. In one of the papers included in this thesis, we investigated the contribution of the binding of complement regulatory proteins factor H (FH) and factor H like protein-1 (FHL-1) to M5 protein. Surprisingly, FH/FHL-1 binding affects neither complement deposition nor phagocytosis resistance. In another paper, we investigated the binding between M and M-like proteins of the M1 serotype and ?2-glycoprotein I (?2-GPI). Fragments of ?2-GPI were shown to be antibacterial, and we found that the interaction of M1 protein and protein H with full-length ?2-GPI inhibited the cleavage into potentially harmful fragments of the plasma protein. In addition, M1 protein and protein H were able to neutralize the effect of the ?2-GPI antibacterial fragments in vitro.



In immune donors, streptococci are opsonized by specific antibodies and subsequently killed. Our results show that these neutralizing antibodies are directed to the N-terminal of the M protein and that they mediated killing by complement activation. We also found that surface deposited C3b binds to complement receptor 3 (CR3) on PMNs which leads to activation of Cdc 42 and Rac 2 that starts the phagocytosis process and triggers the induction of oxidative burst. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Potempa, Jan, Department of Microbiology, Jagellonian University, Krakow, Poland and Department of Biochemistry, U
organization
publishing date
type
Thesis
publication status
published
subject
keywords
M protein, Streptococcus pyogenes, Streptolysin O, The complement system, Neutrophils, Biomedical sciences, Biomedicinska vetenskaper, General biomedical sciences, Biomedicinska vetenskaper (allmänt), Microbiology, transplantation, Immunology, serology, mykologi, virologi, bakteriologi, Mikrobiologi, mycology, virology, Immunologi, serologi, Infections, Infektioner, Clinical biology, Klinisk biologi, bacteriology
pages
150 pages
publisher
Department of Clinical Sciences, Lund University
defense location
GK-salen, Biomedicinskt Centrum, Sölvegatan 19
defense date
2005-12-09 09:30:00
ISBN
91-85481-13-0
language
English
LU publication?
yes
additional info
Maria Nilsson, Maria Weineisen, Tommy Andersson, Lennart Truedsson and Ulf Sjöbring. 2005. Critical role for complement receptor 3 (CD11b/CD18), but not for Fc receptors, in killning of Streptococcus pyogenes by neutrophils in human immune serum European Journal of Immunology, vol 35 pp 1472-1481. Department of Clinical Sciences
Maria Nilsson, Ole Sorensen, Matthias Mörgelin, Maria Weineisen, Ulf Sjöbring and Heiko Herwald. 2005. Activation of human polymorphonuclear neutrophils by Streptolysin O from Streptococccus pyogenes leads to the release of pro-inflammatory mediators Department of clinical sciences (submitted)
Maria Nilsson, Sylvia Vasylic, Matthias Mörgelin, Joost Meiers, Philip de Groot and Heiko Herwald. 2005. The antibacterial activity of peptides derived from human beta-2 glycoprotein I is neutralized by protein H and M1 protein from Streptococcus pyogenes Department of clinical sciences (manuscript)
Heike Kotarsky, Maria Nilsson, Henrik Svensson, Peter Zipfel, Lennart Truedsson and Ulf Sjöbring. 2001. Group A streptococcal phagocytosis resistance is independent of complement factor H and factor H-like protein I binding Molecular microbiology, vol 41 pp 817-826. Department of clinical sciences
id
50c150a8-d831-4ad3-92f1-b51c7bf14a77 (old id 545777)
date added to LUP
2016-04-01 17:13:56
date last changed
2018-11-21 20:47:40
@phdthesis{50c150a8-d831-4ad3-92f1-b51c7bf14a77,
  abstract     = {{Streptococcus pyogenes is an important human pathogen frequently colonizing the throat and skin of humans. To facilitate colonization and spread and to avoid the host immune defence, streptococci are endowed with a variety of virulence factors, two of which are investigated in this thesis namely streptolysin O (SLO) and M protein.<br/><br>
<br/><br>
SLO is a secreted cytolysin that forms pores in eukaryotic membranes by binding to cholesterol. This thesis shows that SLO, via calcium and p38 MAPK, stimulates polymorphonuclear neutrophilic granulocytes (PMNs) to release the pro-inflammatory mediators heparin binding protein (HBP), LL-37, ?-defensin, and elastase. This will lead to an exaggerated immune response that may be beneficial to streptococci and could explain some of the symptoms of severe streptococcal infections.<br/><br>
<br/><br>
M proteins form a family of membrane anchored surface proteins that project from the streptococcal surface and have been linked to the characteristic feature of S. pyogenes to escape phagocytosis. The exact mechanisms underlying this phagocytosis resistance remain unknown. In one of the papers included in this thesis, we investigated the contribution of the binding of complement regulatory proteins factor H (FH) and factor H like protein-1 (FHL-1) to M5 protein. Surprisingly, FH/FHL-1 binding affects neither complement deposition nor phagocytosis resistance. In another paper, we investigated the binding between M and M-like proteins of the M1 serotype and ?2-glycoprotein I (?2-GPI). Fragments of ?2-GPI were shown to be antibacterial, and we found that the interaction of M1 protein and protein H with full-length ?2-GPI inhibited the cleavage into potentially harmful fragments of the plasma protein. In addition, M1 protein and protein H were able to neutralize the effect of the ?2-GPI antibacterial fragments in vitro.<br/><br>
<br/><br>
In immune donors, streptococci are opsonized by specific antibodies and subsequently killed. Our results show that these neutralizing antibodies are directed to the N-terminal of the M protein and that they mediated killing by complement activation. We also found that surface deposited C3b binds to complement receptor 3 (CR3) on PMNs which leads to activation of Cdc 42 and Rac 2 that starts the phagocytosis process and triggers the induction of oxidative burst.}},
  author       = {{Nilsson, Maria E}},
  isbn         = {{91-85481-13-0}},
  keywords     = {{M protein; Streptococcus pyogenes; Streptolysin O; The complement system; Neutrophils; Biomedical sciences; Biomedicinska vetenskaper; General biomedical sciences; Biomedicinska vetenskaper (allmänt); Microbiology; transplantation; Immunology; serology; mykologi; virologi; bakteriologi; Mikrobiologi; mycology; virology; Immunologi; serologi; Infections; Infektioner; Clinical biology; Klinisk biologi; bacteriology}},
  language     = {{eng}},
  publisher    = {{Department of Clinical Sciences, Lund University}},
  school       = {{Lund University}},
  title        = {{Interactions between Streptococcus pyogenes and the human immune defence}},
  year         = {{2005}},
}