Evasion of human innate and acquired immunity by a bacterial homolog of CD11b that inhibits opsonophagocytosis.
Nat Med
; 7(12): 1298-305, 2001 Dec.
Article
em En
| MEDLINE
| ID: mdl-11726969
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fagocitose
/
Infecções Estreptocócicas
/
Streptococcus pyogenes
/
Proteínas de Bactérias
/
Proteínas Opsonizantes
/
Integrinas
/
Antígeno de Macrófago 1
Tipo de estudo:
Prognostic_studies
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article