title: Leptospiral immunoglobulin-like proteins interact with human complement regulators factor H, FHL-1, FHR-1, and C4BP.
abstract: 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.
authors.affiliation: Department of Immunology, University of São Paulo, Sao Paulo, Brazil.
authors.forename: Mónica Marcela
authors.initials: MM
authors.lastname: Castiblanco-Valencia
authors.forename: Tatiana Rodrigues
authors.initials: TR
authors.lastname: Fraga
authors.forename: Ludmila Bezerra da
authors.initials: LB
authors.lastname: Silva
authors.forename: Denize
authors.initials: D
authors.lastname: Monaris
authors.forename: Patrícia Antônia Estima
authors.initials: PA
authors.lastname: Abreu
authors.forename: Stefanie
authors.initials: S
authors.lastname: Strobel
authors.forename: Mihály
authors.initials: M
authors.lastname: Józsi
authors.forename: Lourdes
authors.initials: L
authors.lastname: Isaac
authors.forename: Angela Silva
authors.initials: AS
authors.lastname: Barbosa
mesh_terms: D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D001798:Blood Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D003179:Complement C3b / Q000378:metabolism; D003180:Complement C3b Inactivator Proteins / Q000378:metabolism*; D050716:Complement C4b-Binding Protein / Q000378:metabolism; D017242:Complement Factor H / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D006649:Histocompatibility Antigens / Q000378:metabolism*; D006801:Humans; D057131:Immune Evasion; D007136:Immunoglobulins / Q000737:chemistry; D007919:Leptospira / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D007922:Leptospirosis / Q000276:immunology* / Q000382:microbiology; D010957:Plasmids
chemical_list: D001426:Bacterial Proteins; D001798:Blood Proteins; C055609:C4BPA protein, human; C493495:CFH protein, human; C517621:CFHR1 protein, human; D003180:Complement C3b Inactivator Proteins; D050716:Complement C4b-Binding Protein; D006649:Histocompatibility Antigens; D007136:Immunoglobulins; C100631:factor H-related protein 1; D003179:Complement C3b; D017242:Complement Factor H