Pleiotropic effects of cell wall amidase LytA on Streptococcus pneumoniae sensitivity to the host immune response.
Infect Immun
; 83(2): 591-603, 2015 Feb.
Article
em En
| MEDLINE
| ID: mdl-25404032
ABSTRACT
The complement system is a key component of the host immune response for the recognition and clearance of Streptococcus pneumoniae. In this study, we demonstrate that the amidase LytA, the main pneumococcal autolysin, inhibits complement-mediated immunity independently of effects on pneumolysin by a complex process of impaired complement activation, increased binding of complement regulators, and direct degradation of complement C3. The use of human sera depleted of either C1q or factor B confirmed that LytA prevented activation of both the classical and alternative pathways, whereas pneumolysin inhibited only the classical pathway. LytA prevented binding of C1q and the acute-phase protein C-reactive protein to S. pneumoniae, thereby reducing activation of the classical pathway on the bacterial surface. In addition, LytA increased recruitment of the complement downregulators C4BP and factor H to the pneumococcal cell wall and directly cleaved C3b and iC3b to generate degradation products. As a consequence, C3b deposition and phagocytosis increased in the absence of LytA and were markedly enhanced for the lytA ply double mutant, confirming that a combination of LytA and Ply is essential for the establishment of pneumococcal pneumonia and sepsis in a murine model of infection. These data demonstrate that LytA has pleiotropic effects on complement activation, a finding which, in combination with the effects of pneumolysin on complement to assist with pneumococcal complement evasion, confirms a major role of both proteins for the full virulence of the microorganism during septicemia.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Infecções Pneumocócicas
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Streptococcus pneumoniae
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Complemento C3
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Parede Celular
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Ativação do Complemento
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Interações Hospedeiro-Patógeno
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N-Acetil-Muramil-L-Alanina Amidase
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article