| Autor: |
Alex González-Alsina, Héctor Martín-Merinero, Margalida Mateu-Borrás, María Verd, Antonio Doménech-Sánchez, Joanna B. Goldberg, Santiago Rodríguez de Córdoba, Sebastián Albertí |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Frontiers in Cellular and Infection Microbiology, Vol 14 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2235-2988 |
| DOI: |
10.3389/fcimb.2024.1328185 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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