title: Pathogenic Leptospira species acquire factor H and vitronectin via the surface protein LcpA.
abstract: Upon infection, pathogenic Leptospira species bind several complement regulators in order to overcome host innate immunity. We previously characterized a 20-kDa leptospiral surface protein which interacts with C4b binding protein (C4BP): leptospiral complement regulator-acquiring protein A (LcpA). Here we show that LcpA also interacts with human factor H (FH), which remains functionally active once bound to the protein. Antibodies directed against short consensus repeat 20 (SCR20) inhibited binding of FH to LcpA by approximately 90%, thus confirming that this particular domain is involved in the interaction. We have also shown for the first time that leptospires bind human vitronectin and that the interaction is mediated by LcpA. Coincubation with heparin blocked LcpA-vitronectin interaction in a dose-dependent manner, strongly suggesting that binding may occur through the heparin binding domains of vitronectin. LcpA also bound to the terminal pathway component C9 and inhibited Zn(2+)-induced polymerization and membrane attack complex (MAC) formation. Competitive binding assays indicated that LcpA interacts with C4BP, FH, and vitronectin through distinct sites. Taken together, our findings indicate that LcpA may play a role in leptospiral immune evasion.
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Ludmila Bezerra
authors.initials: LB
authors.lastname: da Silva
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Lidia Dos Santos
authors.initials: Ldos S
authors.lastname: Miragaia
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Leandro Carvalho Dantas
authors.initials: LC
authors.lastname: Breda
authors.affiliation: Laboratório de Biologia Celular, Instituto Butantan, São Paulo, Brazil.
authors.forename: Cecilia Mari
authors.initials: CM
authors.lastname: Abe
authors.affiliation: Laboratório de Biofármacos em Células Animais, Instituto Butantan, São Paulo, Brazil.
authors.forename: Mariana Costa Braga
authors.initials: MC
authors.lastname: Schmidt
authors.affiliation: Laboratório de Biofármacos em Células Animais, Instituto Butantan, São Paulo, Brazil.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Moro
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Denize
authors.initials: D
authors.lastname: Monaris
authors.affiliation: Laboratório de Genômica Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Jonas Nascimento
authors.initials: JN
authors.lastname: Conde
authors.affiliation: MTA-ELTE Lendület Complement Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Mihály
authors.initials: M
authors.lastname: Józsi
authors.affiliation: Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Isaac
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil.
authors.forename: Patrícia Antônia Estima
authors.initials: PA
authors.lastname: Abreu
authors.affiliation: Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil angela.barbosa@butantan.gov.br.
authors.forename: Angela Silva
authors.initials: AS
authors.lastname: Barbosa
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology; D001665:Binding Sites; D001667:Binding, Competitive; D003167:Complement Activation; D050716:Complement C4b-Binding Protein / Q000737:chemistry / Q000276:immunology; D003186:Complement C9 / Q000737:chemistry / Q000276:immunology; D017242:Complement Factor H / Q000737:chemistry / Q000276:immunology; D015938:Complement Membrane Attack Complex / Q000737:chemistry; D006493:Heparin / Q000737:chemistry; D006801:Humans; D057131:Immune Evasion; D007919:Leptospira / Q000737:chemistry* / Q000276:immunology / Q000472:pathogenicity; D007921:Leptospira interrogans / Q000737:chemistry* / Q000276:immunology / Q000472:pathogenicity; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000276:immunology; D011485:Protein Binding; D019096:Vitronectin / Q000737:chemistry* / Q000276:immunology; D015032:Zinc / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; C055609:C4BPA protein, human; C493495:CFH protein, human; D050716:Complement C4b-Binding Protein; D003186:Complement C9; D015938:Complement Membrane Attack Complex; D010446:Peptide Fragments; D019096:Vitronectin; D017242:Complement Factor H; D006493:Heparin; D015032:Zinc