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


Autoria(s): Castiblanco-Valencia, Monica Marcela; Fraga, Tatiana Rodrigues; da Silva, Ludmila Bezerra; Monaris, Denize; Estima Abreu, Patricia Antonia; Strobel, Stefanie; Jozsi, Mihaly; Isaac, Lourdes; Barbosa, Angela Silva
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

05/11/2013

05/11/2013

2012

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.

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2010/50043-0]

Fundacao de Amparo a Pesquisa do Estado de Sao Paulo

Identificador

JOURNAL OF INFECTIOUS DISEASES, CARY, v. 205, n. 6, supl. 1, Part 3, pp. 995-1004, 42064, 2012

0022-1899

http://www.producao.usp.br/handle/BDPI/41898

10.1093/infdis/jir875

http://dx.doi.org/10.1093/infdis/jir875

Idioma(s)

eng

Publicador

OXFORD UNIV PRESS INC

CARY

Relação

JOURNAL OF INFECTIOUS DISEASES

Direitos

restrictedAccess

Copyright OXFORD UNIV PRESS INC

Palavras-Chave #PROTECTIVE IMMUNITY #BINDING-PROTEIN #C4B-BINDING PROTEIN #EXPRESSION VECTOR #C3B INACTIVATOR #C-TERMINUS #INTERROGANS #LIGB #FIBRONECTIN #SERUM #IMMUNOLOGY #INFECTIOUS DISEASES #MICROBIOLOGY
Tipo

article

original article

publishedVersion