Pathogenic Leptospira species acquire factor H and vitronectin via the surface protein LcpA.

Autor:	da Silva LB; Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil., Miragaia Ldos S; Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil., Breda LC; Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil., Abe CM; Laboratório de Biologia Celular, Instituto Butantan, São Paulo, Brazil., Schmidt MC; Laboratório de Biofármacos em Células Animais, Instituto Butantan, São Paulo, Brazil., Moro AM; Laboratório de Biofármacos em Células Animais, Instituto Butantan, São Paulo, Brazil., Monaris D; Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil., Conde JN; Laboratório de Genômica Estrutural, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Józsi M; MTA-ELTE Lendület Complement Research Group, Department of Immunology, Eötvös Loránd University, Budapest, Hungary., Isaac L; Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, Brazil., Abreu PA; Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil., Barbosa AS; Laboratório de Bacteriologia, Instituto Butantan, São Paulo, Brazil angela.barbosa@butantan.gov.br.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2015 Mar; Vol. 83 (3), pp. 888-97. Date of Electronic Publication: 2014 Dec 22.
DOI:	10.1128/IAI.02844-14
Abstrakt:	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. (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
Databáze:	MEDLINE
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