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Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis.
- Source :
-
Nature medicine [Nat Med] 2001 Dec; Vol. 7 (12), pp. 1298-305. - Publication Year :
- 2001
-
Abstract
- Microbial pathogens must evade the human immune system to survive, disseminate and cause disease. By proteome analysis of the bacterium Group A Streptococcus (GAS), we identified a secreted protein with homology to the alpha-subunit of Mac-1, a leukocyte beta2 integrin required for innate immunity to invading microbes. The GAS Mac-1-like protein (Mac) was secreted by most pathogenic strains, produced in log-phase and controlled by the covR-covS two-component gene regulatory system, which also regulates transcription of other GAS virulence factors. Patients with GAS infection had titers of antibody specific to Mac that correlated with the course of disease, demonstrating that Mac was produced in vivo. Mac bound to CD16 (FcgammaRIIIB) on the surface of human polymorphonuclear leukocytes and inhibited opsonophagocytosis and production of reactive oxygen species, which resulted in significantly decreased pathogen killing. Thus, by mimicking a host-cell receptor required for an innate immune response, the GAS Mac protein inhibits professional phagocyte function by a novel strategy that enhances pathogen survival, establishment of infection and dissemination.
- Subjects :
- Acute Disease
Amino Acid Sequence
Antibodies, Bacterial blood
Binding Sites
Convalescence
Integrins genetics
Macrophage-1 Antigen genetics
Macrophage-1 Antigen metabolism
Models, Immunological
Molecular Sequence Data
Neutrophils drug effects
Pharyngitis immunology
Protein Binding
Reactive Oxygen Species metabolism
Receptors, IgG metabolism
Rheumatic Fever immunology
Sequence Homology, Amino Acid
Bacterial Proteins
Integrins metabolism
Macrophage-1 Antigen pharmacology
Opsonin Proteins
Phagocytosis drug effects
Streptococcal Infections immunology
Streptococcus pyogenes pathogenicity
Subjects
Details
- Language :
- English
- ISSN :
- 1078-8956
- Volume :
- 7
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Nature medicine
- Publication Type :
- Academic Journal
- Accession number :
- 11726969
- Full Text :
- https://doi.org/10.1038/nm1201-1298