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Streptococcal M5 protein prevents neutrophil phagocytosis by interfering with CD11b/CD18 receptor-mediated association and signaling.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2004 Mar 15; Vol. 172 (6), pp. 3798-807. - Publication Year :
- 2004
-
Abstract
- 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 (DeltaM5), but not the wild-type parent strain (M5). After 3 h, 3-4 times as many DeltaM5 as M5 bacteria were associated with the neutrophils, and more DeltaM5 than M5 bacteria were ingested. However, there was no statistically significant difference between DeltaM5 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 DeltaM5 bacteria, whereas the blocking of two other complement receptors, CD11c/CD18 (CR4) and CD35 (CR1), did not. The CD11b/CD18-mediated killing of DeltaM5 bacteria resulted in protein tyrosine phosphorylations and Cdc42 activation. Furthermore, inhibition of CD11b/CD18 receptor engagement or tyrosine kinase activity blocked the DeltaM5-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.
- Subjects :
- Antibodies, Blocking pharmacology
Antigens, Bacterial genetics
Bacterial Adhesion immunology
Bacterial Outer Membrane Proteins genetics
CD11b Antigen immunology
CD18 Antigens immunology
Carrier Proteins genetics
Complement Activation immunology
Humans
Immunosuppressive Agents pharmacology
Neutrophils metabolism
Phosphorylation
Protein-Tyrosine Kinases physiology
Receptors, Complement antagonists & inhibitors
Receptors, Complement physiology
Streptococcus pyogenes genetics
Tyrosine metabolism
cdc42 GTP-Binding Protein metabolism
rac GTP-Binding Proteins metabolism
RAC2 GTP-Binding Protein
Antigens, Bacterial physiology
Bacterial Outer Membrane Proteins physiology
CD11b Antigen physiology
CD18 Antigens physiology
Carrier Proteins physiology
Neutrophils immunology
Neutrophils microbiology
Phagocytosis immunology
Signal Transduction immunology
Streptococcus pyogenes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 172
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15004185
- Full Text :
- https://doi.org/10.4049/jimmunol.172.6.3798