Leptospiral Immunoglobulin-like Proteins Interact With Human Complement Regulators Factor H, FHL-1, FHR-1, and C4BP

• Published in: The Journal of infectious diseases 2012-03, Vol.205 (6), p.995-1004
• Main Authors: Castiblanco-Valencia, Mónica Marcela, Fraga, Tatiana Rodrigues, da Silva, Ludmila Bezerra, Monaris, Denize, Abreu, Patrícia Antônia Estima, Strobel, Stefanie, Józsi, Mihály, Isaac, Lourdes, Barbosa, Angela Silva
• Format: Article
• Language: English
• Subjects: Antibodies; BACTERIA; Bacterial Adhesion; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Binding Sites; Biological and medical sciences; Blood Proteins - metabolism; Carrier proteins; Cloning, Molecular; Complement C3b - metabolism; Complement C3b Inactivator Proteins - metabolism; Complement C4b-Binding Protein - metabolism; Complement Factor H - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Bacterial; Histocompatibility Antigens - metabolism; Humans; Immune Evasion; Immunoglobulins - chemistry; Infectious diseases; Leptospira; Leptospira - genetics; Leptospira - metabolism; Leptospira - pathogenicity; Leptospirosis - immunology; Leptospirosis - microbiology; Medical sciences; Microbiology; Molecular interactions; Molecules; Monoclonal antibodies; Physiological regulation; Plasmids; Proteins; Recombinant proteins
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jir875

Leptospira, the causative agent of leptospirosis, interacts with several host molecules, including extracellular matrix components, coagulation cascade proteins, and human complement regulators. Here we demonstrate that acquisition of factor H (FH) on the Leptospira surface is crucial for bacterial survival in the serum and that these spirochetes, besides interacting with FH, FH related-1, and C4b binding protein (C4BP), also acquire FH like-1 from human serum. We also demonstrate that binding to these complement regulators is mediated by leptospiral immunoglobulin-like (Lig) proteins, previously shown to interact with fibronectin, laminin, collagen, elastin, tropoelastin, and fibrinogen. Factor H binds to Lig proteins via short consensus repeat domains 5 and 20. Competition assays suggest that FH and C4BP have distinct binding sites on Lig proteins.Moreover, FH and C4BP bound to immobilized Ligs display cofactor activity, mediating C3b and C4b degradation by factor I. In conclusion, Lig proteins are multifunctional molecules, contributing to leptospiral adhesion and immune evasion.