학술논문
Factor H-related protein 1 promotes complement-mediated opsonization of Pseudomonas aeruginosa .
Document Type
Academic Journal
Author
González-Alsina A; Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Universidad de las Islas Baleares and Instituto de Investigación Sanitaria de les Illes Balears (IDISBA), Palma de Mallorca, Spain.; Martín-Merinero H; Center for Biological Research-Margarita Salas and Centro Investigación Biomédica En Red (CIBER) de Enfermedades Raras, Madrid, Spain.; Mateu-Borrás M; Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Universidad de las Islas Baleares and Instituto de Investigación Sanitaria de les Illes Balears (IDISBA), Palma de Mallorca, Spain.; Verd M; Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Universidad de las Islas Baleares and Instituto de Investigación Sanitaria de les Illes Balears (IDISBA), Palma de Mallorca, Spain.; Doménech-Sánchez A; Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Universidad de las Islas Baleares and Instituto de Investigación Sanitaria de les Illes Balears (IDISBA), Palma de Mallorca, Spain.; Goldberg JB; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, United States.; Rodríguez de Córdoba S; Center for Biological Research-Margarita Salas and Centro Investigación Biomédica En Red (CIBER) de Enfermedades Raras, Madrid, Spain.; Albertí S; Instituto Universitario de Investigación en Ciencias de la Salud (IUNICS), Universidad de las Islas Baleares and Instituto de Investigación Sanitaria de les Illes Balears (IDISBA), Palma de Mallorca, Spain.
Source
Publisher: Frontiers Media SA Country of Publication: Switzerland NLM ID: 101585359 Publication Model: eCollection Cited Medium: Internet ISSN: 2235-2988 (Electronic) Linking ISSN: 22352988 NLM ISO Abbreviation: Front Cell Infect Microbiol Subsets: MEDLINE
Subject
Language
English
Abstract
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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 González-Alsina, Martín-Merinero, Mateu-Borrás, Verd, Doménech-Sánchez, Goldberg, Rodríguez de Córdoba and Albertí.)
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 González-Alsina, Martín-Merinero, Mateu-Borrás, Verd, Doménech-Sánchez, Goldberg, Rodríguez de Córdoba and Albertí.)