Pathogenic Leptospira species acquire factor H and vitronectin via the surface protein LcpA
da Silva, LB; Miragaia, L; Breda, LC; Abe, CM; Schmidt, MC; Moro, AM; Monaris, D; Conde, JN; Józsi, M; Isaac, L; Abreu, PA; Barbosa, AS
HERO ID
2902375
Reference Type
Journal Article
Year
2015
Language
English
PMID
| HERO ID | 2902375 |
|---|---|
| In Press | No |
| Year | 2015 |
| Title | Pathogenic Leptospira species acquire factor H and vitronectin via the surface protein LcpA |
| Authors | da Silva, LB; Miragaia, L; Breda, LC; Abe, CM; Schmidt, MC; Moro, AM; Monaris, D; Conde, JN; Józsi, M; Isaac, L; Abreu, PA; Barbosa, AS |
| Journal | Infection and Immunity |
| Volume | 83 |
| Issue | 3 |
| Page Numbers | 888-897 |
| 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. |
| Doi | 10.1128/IAI.02844-14 |
| Pmid | 25534939 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |