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

Autor(es)

Castiblanco-Valencia, Monica Marcela ^[1] ; Fraga, Tatiana Rodrigues ^[1] ; da Silva, Ludmila Bezerra ^[2] ; Monaris, Denize ^[2] ; Estima Abreu, Patricia Antonia ^[2] ; Strobel, Stefanie ^[3] ; Jozsi, Mihaly ^[3] ; Isaac, Lourdes ^[1] ; Barbosa, Angela Silva ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Imunol, Inst Ciencias Biomed, BR-05508900 Sao Paulo - Brazil

^[2] Butantan Inst, Bacteriol Lab, Sao Paulo - Brazil

^[3] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Jr Res Grp Cellular Immunobiol, Jena - Germany

• Tipo de documento: Artigo Científico
• Fonte: Journal of Infectious Diseases; v. 205, n. 6, p. 995-1004, MAR 15 2012.
• Citações Web of Science: 68

Resumo

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. (AU)

• Processo FAPESP: 10/50043-0 - Sistema complemento e patogenicidade de leptospiras: mecanismos de ativação e escape identificação de ligantes bacterianos, caracterização de proteases e estabelecimento de modelo murino in vivo
• Beneficiário: Lourdes Isaac
• Modalidade de apoio: Auxílio à Pesquisa - Temático