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

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• 作者：Mó ; nica Marcela Castiblanco-Valencia^a ; Tatiana Rodrigues Fraga^a ; Ana Helena Pagotto^b ; Solange Maria de Toledo Serrano^b ; Patricia Antonia Estima Abreu^c ; Angela Silva Barbosa^c ; Lourdes Isaac^a ; ^{louisaac@icb.usp.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Leptospira ; Complement ; Immune evasion ; Lig proteins ; Plasminogen
• 刊名：Immunobiology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：221
• 期：5
• 页码：679-689
• 全文大小：2695 K

文摘

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.