Factor H-related protein 1 promotes complement-mediated opsonization of .

Pseudomonas aeruginosa is an important human opportunistic pathogen responsible for a wide range of infections. The complement system is the main early host defense mechanism to control these infections. P. aeruginosa counteracts complement attack by binding Factor H (FH), a complement regulator tha...

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Detalles Bibliográficos
Autores: Gonzalez-Alsina, Alex, Martín-Merinero, Héctor, Mateu-Borrás, Margalida, Verd, María, Doménech-Sánchez, Antonio, Goldberg, Joanna B, Rodríguez de Córdoba, Santiago, Alberti, Sebastian
Tipo de recurso: artículo
Fecha de publicación:2024
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/24958
Acceso en línea:https://hdl.handle.net/20.500.13003/24958
Access Level:acceso abierto
Palabra clave:Pseudomonas aeruginosa
Complement Factor H
Factor H de Complemento
FHR-1
OprG
P. aeruginosa
complement system
factor H
Descripción
Sumario:Pseudomonas aeruginosa is an important human opportunistic pathogen responsible for a wide range of infections. The complement system is the main early host defense mechanism to control these infections. P. aeruginosa counteracts complement attack by binding Factor H (FH), a complement regulator that inactivates C3b, preventing the formation of the C3-convertase and complement amplification on the bacterial surface. Factor H-related proteins (FHRs) are a group of plasma proteins evolutionarily related to FH that have been postulated to interfere in this bacterial mechanism of resisting complement. Here, we show that FHR-1 binds to P. aeruginosa via the outer membrane protein OprG in a lipopolysaccharide (LPS) O antigen-dependent manner. Binding assays with purified components or with FHR-1-deficient serum supplemented with FHR-1 show that FHR-1 competes with FH for binding to P. aeruginosa. Blockage of FH binding to C3b deposited on the bacteria reduces FH-mediated cofactor activity of C3b degradation, increasing the opsonization of the bacteria and the formation of the potent chemoattractant C5a. Overall, our findings indicate that FHR-1 is a host factor that promotes complement activation, facilitating clearance of P. aeruginosa by opsonophagocytosis.