Immune evasion of Borrelia burgdorferi by acquisition of human complement regulators FHL-1/reconectin and Factor H

• Verfasst von: Kraiczy, Peter [VerfasserIn]
• Verfasst von: Skerka, Christine [VerfasserIn]
• Verfasst von: Kirschfink, Michael [VerfasserIn]
• Verfasst von: Brade, Volker [VerfasserIn]
• Verfasst von: Zipfel, Peter F. [VerfasserIn]
• Titel: Immune evasion of Borrelia burgdorferi by acquisition of human complement regulators FHL-1/reconectin and Factor H
• Verf.angabe: Peter Kraiczy, Christine Skerka, Michael Kirschfink, Volker Brade and Peter F. Zipfel
• E-Jahr: 2001
• Jahr: 16 May 2001
• Umfang: 11 S.
• Fussnoten: Gesehen am 17.02.2021
• Titel Quelle: Enthalten in: European journal of immunology
• Ort Quelle: Weinheim : Wiley-VCH, 1971
• Jahr Quelle: 2001
• Band/Heft Quelle: 31(2001), 6, Seite 1674-1684
• ISSN Quelle: 1521-4141
• DOI: doi:10.1002/1521-4141(200106)31:6<1674::aid-immu1674>3.0.co;2-2
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adsorption
• Sach-SW: Bacterial Proteins
• Sach-SW: Binding Sites
• Sach-SW: Blood Proteins
• Sach-SW: Borrelia burgdorferi Group
• Sach-SW: Complement Activation
• Sach-SW: Complement C3b
• Sach-SW: Complement C3b Inactivator Proteins
• Sach-SW: Complement Factor H
• Sach-SW: Humans
• Sach-SW: Lyme Disease
• K10plus-PPN: 1748486799

Abstract

To understand immune evasion mechanisms of Borrelia burgdorferi we compared serum-resistant B. afzelii and serum-sensitive B. garinii isolates for their capacity toacquire human complement regulators. Here we demonstrate that the two borrelial genospecies show different binding of the two important human complement regulators, FHL-1/reconectin and Factor H. All serum-resistant B. afzelii isolates bound FHL-1/reconectin and also Factor H, and all analyzed serum-sensitive B. garinii isolates showed no or a significantly lower binding activity. Using recombinant deletion mutants, the binding domains were localized to the C terminus of FHL-1/reconectin to short consensus repeats 5-7. The borrelial binding proteins were located in the surface of the bacteria as demonstrated by immunofluorescence staining of intact, serum-exposed bacteria and by enrichment of outer membrane proteins. The surface-attached complement regulators maintained complement regulatory activity as demonstrated in a cofactor assay. By ligand blotting two different borrelial binding proteins were identified that were responsible for the surface attachment of FHL-1/reconectin and Factor H. These borrelial complement regulators acquiring surface proteins (CRASP) were further characterized as either CRASP-1, a 27.5-kDa molecule which preferentially binds FHL-1/reconectin and which was present in all serum-resistant borreliae, or CRASP-2, a 20/21-kDa protein which interacts preferentially with Factor H and the expression of which was more restricted, being detected in four of the six isolates analyzed. In summary, we describe a new immune evasion mechanism of B. burgdorferi, as these bacteria acquire human complement regulators to control complement activation on their surface and to prevent formation of toxic activation products.