| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Experimental Pathology, Lund University, Malmö University Hospital, Malmö, Sweden;
Microbiology, Immunology, and Glycobiology, Lund University, Lund, Sweden; and
Molecular Biology, Umeå University, Umeå, Sweden
Group A streptococci (GAS) are common human pathogens that express major surface-associated virulence factors designated M proteins. In this study, we explored directly the cellular mechanisms behind their supposed ability to prevent phagocytosis. Isolated human neutrophils killed an M-negative GAS mutant (
M5), but not the wild-type parent strain (M5). After 3 h, 3–4 times as many M5 as M5 bacteria were associated with the neutrophils, and more M5 than M5 bacteria were ingested. However, there was no statistically significant difference between M5 and M5 bacteria in regard to the percentage of the neutrophil-associated bacteria that were ingested, indicating that M5 protein prevents an adhesion receptor-dependent association with neutrophils and not the phagocytic machinery per se. Different Abs against CD11b/CD18 (CR3) blocked adhesion and killing of M5 bacteria, whereas the blocking of two other complement receptors, CD11c/CD18 (CR4) and CD35 (CR1), did not. The CD11b/CD18-mediated killing of M5 bacteria resulted in protein tyrosine phosphorylations and Cdc42 activation. Furthermore, inhibition of CD11b/CD18 receptor engagement or tyrosine kinase activity blocked the M5-induced activation of Cdc42 as well as the killing of these bacteria. We conclude that M5 protein interferes with the CD11b/CD18-dependent association between GAS and neutrophils, and thereby blocks subsequent ingestion of the bacteria.
This article has been cited by other articles:
|
|
 |
|
  L. I. Pahlman, E. Malmstrom, M. Morgelin, and H. Herwald M protein from Streptococcus pyogenes induces tissue factor expression and pro-coagulant activity in human monocytes Microbiology, August 1, 2007; 153(8): 2458 - 2464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ben Nasr, J. Haithcoat, J. E. Masterson, J. S. Gunn, T. Eaves-Pyles, and G. R. Klimpel Critical role for serum opsonins and complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in phagocytosis of Francisella tularensis by human dendritic cells (DC): uptake of Francisella leads to activation of immature DC and intracellular survival of the bacteria J. Leukoc. Biol., October 1, 2006; 80(4): 774 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. I. Pahlman, M. Morgelin, J. Eckert, L. Johansson, W. Russell, K. Riesbeck, O. Soehnlein, L. Lindbom, A. Norrby-Teglund, R. R. Schumann, et al. Streptococcal M Protein: A Multipotent and Powerful Inducer of Inflammation J. Immunol., July 15, 2006; 177(2): 1221 - 1228. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
