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Mjusko THESIS APPROVED Complement evasion strategies of human pathogens - the evolutionary arms race Jusko, Monika 2014 Link to publication Citation for published version (APA): Jusko, M. (2014). Complement evasion strategies of human pathogens - the evolutionary arms race. Protein Chemistry, Lund University. 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LUND UNIVERSITY PO Box 117 221 00 Lund +46 46-222 00 00 Download date: 09. Oct. 2021 Complement Evasion Strategies of Human Pathogens The evolutionary arms race Monika Jusko Department of Laboratory Medicine Malmö Division of Medical Protein Chemistry Faculty of Medicine, Lund University Malmö, Sweden [email protected] Doctoral dissertation Academic thesis, which by due permission of the Faculty of Medicine, Lund University, Sweden will be publicly defended in Lilla Aulan, Jan Waldenströmsgata 5, Malmö on Friday 5th of September 2014 at 9:00 Faculty opponent Professor George Hajishengallis Department of Microbiology, University of Pennsylvania, School of Dental Medicine, Philadelphia, USA Complement Evasion Strategies of Human Pathogens The evolutionary arms race Monika Jusko Cover image: Complement protein complexes: C1 complex (left), MBL-MASPs (middle), Membrane attack complex (right) Copyright © Monika Jusko Lund University, Faculty of Medicine Doctoral Dissertation Series 2014:91 ISBN 978-91-7619-020-3 ISSN 1652-8220 Printed in Sweden by Media-Tryck, Lund University Lund 2014 "Out of life's school of war: what does not destroy me, makes me stronger." F. Nietzsche Table of Content TABLE OF CONTENT .................................................................................................... 7 LIST OF PAPERS ............................................................................................................ 9 ABBREVIATIONS ........................................................................................................ 10 INTRODUCTION .......................................................................................................... 11 SCOPE OF THE STUDIES INCLUDED IN THIS THESIS: ...................................................... 12 OUR IMMUNE SYSTEM .............................................................................................. 14 INNATE AND ADAPTIVE IMMUNITY ................................................................................ 14 PHYSICAL BARRIERS ....................................................................................................... 14 TLRS AND NODS/NLRS ................................................................................................ 15 COMPLEMENT SYSTEM AND ITS ACTIVATION PATHWAYS ............................................. 17 THE ALTERNATIVE PATHWAY ..................................................................................................... 18 THE CLASSICAL AND LECTIN PATHWAYS .................................................................................. 20 COMPLEMENT EFFECTOR MECHANISMS AND ITS INSTRUCTIVE FUNCTIONS IN GENERATION OF ADAPTIVE IMMUNITY .......................................................................... 23 THE MAC FORMATION – DIRECT LYSIS OF MICROORGANISMS .............................................. 23 ANAPHYLATOXINS – MEDIATORS OF INFLAMMATION ............................................................ 24 OPSONIZATION - FACILITATING UPTAKE OF COMPLEMENT TARGETS BY DIFFERENT IMMUNE CELLS ................................................................................................................................ 27 OTHER FUNCTIONS OF COMPLEMENT IN ORCHESTRATING ADAPTIVE IMMUNITY .............. 30 REGULATION OF COMPLEMENT ...................................................................................... 31 NOVEL FUNCTIONS OF COMPLEMENT REGULATORS ................................................................ 34 PERIODONTAL DISEASE .......................................................................................... 36 PERIODONTITIS FORMS AND PREVALENCE .................................................................... 36 HUMAN ORAL CAVITY AS A MICROBIAL HABITAT .......................................................... 38 HISTORICAL PERSPECTIVE ON THE IDENTIFICATION AND CLASSIFICATION OF ORAL BACTERIA ......................................................................................................................... 39 THE EMERGING PERIODONTAL PATHOGENS .................................................................. 41 CURRENT UNDERSTANDING OF PERIODONTAL DISEASE ............................................... 42 THE CENTRAL ROLE OF COMPLEMENT EVASION BY BACTERIA IN PERIODONTITIS ...... 43 COMPLEMENT INHIBITION BY PERIODONTAL BACTERIA ........................................................ 44 COMPLEMENT ACTIVATION BY PERIODONTAL BACTERIA ....................................................... 46 COMPLEMENT HIJACKING BY PERIODONTAL BACTERIA .......................................................... 46 GAPS IN THE CURRENT UNDERSTANDING OF PERIODONTITIS AND NEW DIRECTIONS IN PERIODONTAL RESEARCH .............................................................................................................. 49 OPPORTUNISTIC PATHOGENS .............................................................................. 55 THE TRANSIENT AND RESIDENT COLONIZERS OF THE SKIN AND MUCOSA ................... 55 THE FEATURES OF S. AUREUS INFECTION ....................................................................... 55 S. AUREUS – THE MASTER OF COMPLEMENT EVASION – THE KNOWN FACTS AND GAPS IN THE UNDERSTANDING OF STAPHYLOCOCCAL INFECTIONS ........................................ 58 STAPHYLOCOCCAL PROTEINS AFFECTING COMPLEMENT AT THE ACTIVATION LEVEL ....... 58 TARGETING THE CENTRAL COMPLEMENT ACTIVATION STEP, C3 CONVERSION, BY STAPHYLOCOCCAL FACTORS ......................................................................................................... 59 MAJOR FINDINGS OF THIS THESIS ....................................................................... 63 PAPERS I AND IV ............................................................................................................. 63 PAPER II .......................................................................................................................... 63 PAPER III ......................................................................................................................... 64 PAPER V .......................................................................................................................... 64 PAPER VI ......................................................................................................................... 65 CONCLUSIONS AND FUTURE PERSPECTIVES .................................................... 66 ACKNOWLEDGEMENTS ............................................................................................ 69 REFERENCES ................................................................................................................ 71 List of Papers The following articles are part of this thesis work and will be referred to in the text with their respective roman numerals: I. Jusko M, Potempa J, Karim AY, Ksiazek M, Riesbeck K, Garred P, Eick S, Blom AM (2012) A metalloproteinase karilysin present in the majority of Tannerella forsythia isolates inhibits all pathways of the complement system. J Immunol. 2012 Mar 1; 188(5):2338-49. II. Jusko M, Potempa J, Kantyka T, Bielecka E, Miller HK, Kalinska M, Dubin G, Garred P, Shaw LN, Blom AM (2013) Staphylococcal proteases aid in evasion of the human complement system. J Innate Immun. 2014;6(1):31-46. III. Malm S, Jusko M, Eick S, Potempa J, Riesbeck K, Blom AM (2012) Acquisition of complement inhibitor serine protease factor I and its cofactors C4b-binding protein and factor H by Prevotella intermedia. PLoS One. 2012; 7(4): e34852. IV. Jusko M, Potempa J, Ksiazek M, Mizgalska D, Riesbeck K, Garred P, Eick S, Blom AM A metalloproteinase mirolysin of Tannerella forsythia inhibits all pathways of the complement system. V. Jusko M, Potempa J, Malm S, Riesbeck K, Eick S, Blom AM Membrane- bound complement inhibitor CD46 guards gingival epithelial cells against periodontal bacteria invasion. VI. Jusko M, Miedziak B, Riesbeck K, Eick S, Potempa J, Blom AM Novel periopathogen Filifactor alocis employs multiple strategies to evade the complement system. Paper I was reprinted with the permission of The American Association of Immunologists, and Paper II – with the permission of Karger Publishers, Basel, Switzerland. 9 Abbreviations APC Antigen presenting cell BCR B-cell receptor CR Complement
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