Plasmin cleaves fibrinogen and the human complement proteins C3b and C5 in the presence of Leptospira interrogans proteins: A new role of LigA and LigB in invasion and complement immune evasion

Author(s)

Castiblanco-Valencia, Monica Marcela ^[1] ; Fraga, Tatiana Rodrigues ^[1] ; Pagotto, Ana Helena ^[2] ; de Toledo Serrano, Solange Maria ^[2] ; Estima Abreu, Patricia Antonia ^[3] ; Barbosa, Angela Silva ^[3] ; Isaac, Lourdes ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[2] Butantan Inst, Ctr Toxins Immune Response & Cell Signaling CeTIC, Special Lab Appl Toxinol, Sao Paulo - Brazil

^[3] Butantan Inst, Bacteriol Lab, Sao Paulo - Brazil

• Document type: Journal article
• Source: Immunobiology; v. 221, n. 5, p. 679-689, MAY 2016.
• Web of Science Citations: 17

Abstract

Plasminogen is a single-chain glycoprotein found in human plasma as the inactive precursor of plasmin. When converted to proteolytically active plasmin, plasmin(ogen) regulates both complement and coagulation cascades, thus representing an important target for pathogenic microorganisms. Leptospira interrogans binds plasminogen, which is converted to active plasmin. Leptospiral immunoglobulin-like (Lig) proteins are surface exposed molecules that interact with extracellular matrix components and complement regulators, including proteins of the FH family and C4BP. In this work, we demonstrate that these multifunctional molecules also bind plasminogen through both N-and C-terminal domains. These interactions are dependent on lysine residues and are affected by ionic strength. Competition assays suggest that plasminogen does not share binding sites with C4BP or FH on Lig proteins at physiological molar ratios. Plasminogen bound to Lig proteins is converted to proteolytic active plasmin in the presence of urokinase-type plasminogen activator (uPA). Lig-bound plasmin is able to cleave the physiological substrates fibrinogen and the complement proteins C3b and C5. Taken together, our data point to a new role of LigA and LigB in leptospiral invasion and complement immune evasion. Plasmin(ogen) acquisition by these versatile proteins may contribute to Leptospira infection, favoring bacterial survival and dissemination inside the host. (C) 2016 Published by Elsevier GmbH. (AU)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 10/50043-0 - Complement system and pathogenicity of Leptospires: mechanisms of activation and evasion, identification of bacterial ligands, characterization of proteases and establishment of an in vivo murine model
• Grantee: Lourdes Isaac
• Support Opportunities: Research Projects - Thematic Grants