Immune evasion in Leptospira: the secretion of proteases that cleave complement proteins

Abstract

Event Abstract Back to Event Immune evasion in Leptospira: the secretion of proteases that cleave complement proteins Tatiana R. Fraga1, Daniella S. Courrol1, Mónica M. Castiblanco-Valencia1, Izaura Y. Hirata2, Luiz Juliano2, Sílvio A. Vasconcellos3, Angela S. Barbosa4 and Lourdes Isaac1* 1 University of São Paulo, Department of Immunology, Brazil 2 Federal University of São Paulo, Department of Biophysics, Brazil 3 University of São Paulo, Faculty of Veterinary Medicine, Brazil 4 Butantan Institute, Laboratory of Bacteriology, Brazil Leptospirosis is a neglected infectious disease of public health importance. The complement system is a major arm of innate immunity. However, pathogenic leptospires have evolved multiple strategies to escape complement attack. In this work we analyzed the ability of leptospires to secrete proteases that cleave and inactivate complement proteins, which could constitute an immune evasion strategy. We demonstrated that the culture supernatant of pathogenic, but not saprophytic leptospires, was able to inhibit the activation of the three complement pathways. Moreover, the supernatant of seven pathogenic strains presented proteolytic activity against C3, C3b and iC3b, proteins from the alternative (Factor B), classical and lectin pathways (C4b and C2). The cleavages were also observed when normal human serum was used. Interestingly, the proteases act together with the host regulators Factor I and Factor H, promoting an efficient inactivation of C3b. Proteolytic fragments of C3 had their N-terminal portion sequenced by Edman degradation. The α-chain cleavage produced 43 kDa (RSSKI-), 47 kDa (YGGGYG-) and 68 kDa bands and the β-chain degradation generates 28 kDa (HPSQKPL-) and 46 kDa fragments. Furthermore, the proteolytic activity was inhibited by 1,10-phenanthroline, indicating the participation of metalloproteases. A recombinant leptospiral metalloprotease from the thermolysin family was produced and cleaved C3 in human serum, suggesting that this protein could be one of the proteases responsible for the effect observed with the whole supernatant. In conclusion, pathogenic leptospiral proteases can deactivate immune effector molecules, and represent potential targets for the development of new therapies and prophylactic approaches in leptospirosis. Keywords: immune evasion of bacteria, complement system, secretion of proteases, Leptospira, Leptospirosis Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Host-pathogen interactions Citation: Fraga TR, Courrol DS, Castiblanco-Valencia MM, Hirata IY, Juliano L, Vasconcellos SA, Barbosa AS and Isaac L (2013). Immune evasion in Leptospira: the secretion of proteases that cleave complement proteins. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00733 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 16 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Lourdes Isaac, University of São Paulo, Department of Immunology, São Paulo, São Paulo, 05508-900, Brazil, louisaac@icb.usp.br Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Tatiana R Fraga Daniella S Courrol Mónica M Castiblanco-Valencia Izaura Y Hirata Luiz Juliano Sílvio A Vasconcellos Angela S Barbosa Lourdes Isaac Google Tatiana R Fraga Daniella S Courrol Mónica M Castiblanco-Valencia Izaura Y Hirata Luiz Juliano Sílvio A Vasconcellos Angela S Barbosa Lourdes Isaac Google Scholar Tatiana R Fraga Daniella S Courrol Mónica M Castiblanco-Valencia Izaura Y Hirata Luiz Juliano Sílvio A Vasconcellos Angela S Barbosa Lourdes Isaac PubMed Tatiana R Fraga Daniella S Courrol Mónica M Castiblanco-Valencia Izaura Y Hirata Luiz Juliano Sílvio A Vasconcellos Angela S Barbosa Lourdes Isaac Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.