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JYVÄSKYLÄ STUDIES IN BIOLOGICAL AND ENVIRONMENTAL SCIENCE

307

Leena Meriläinen

Characterization and Immunological Aspects of Borrelia Burgdorferi Pleomorphic Round Bodies

JYVÄSKYLÄ STUDIES IN BIOLOGICAL AND ENVIRONMENTAL SCIENCE 307

Leena Meriläinen Characterization and Immunological Aspects of Borrelia Burgdorferi Pleomorphic Round Bodies

Esitetään Jyväskylän yliopiston matemaattis-luonnontieteellisen tiedekunnan suostumuksella julkisesti tarkastettavaksi yliopiston Ylistönrinteellä salissa YAA303 lokakuun 23. päivänä 2015 kello 12. Academic dissertation to be publicly discussed, by permission of the Faculty of Mathematics and Science of the University of Jyväskylä, in Ylistönrinne, hall YAA303, on October 23, 2015 at 12 o’clock noon.

UNIVERSITY OF

JYVÄSKYLÄ

JYVÄSKYLÄ 2015

Characterization and Immunological Aspects of Borrelia Burgdorferi Pleomorphic Round Bodies

JYVÄSKYLÄ STUDIES IN BIOLOGICAL AND ENVIRONMENTAL SCIENCE 307

Leena Meriläinen Characterization and Immunological Aspects of Borrelia Burgdorferi Pleomorphic Round Bodies

UNIVERSITY OF

JYVÄSKYLÄ

JYVÄSKYLÄ 2015

Editors Varpu Marjomäki Department of Biological and Environmental Science, University of Jyväskylä Pekka Olsbo, Sini Tuikka Publishing Unit, University Library of Jyväskylä

Jyväskylä Studies in Biological and Environmental Science Editorial Board Jari Haimi, Anssi Lensu, Timo Marjomäki, Varpu Marjomäki Department of Biological and Environmental Science, University of Jyväskylä

Cover pictures: Transmission electron microscopy illustrations of Borrelia burgdorferi spirochete (left) and round body (right). Images by Leena Meriläinen.

URN:ISBN:978-951-39-6335-4 ISBN 978-951-39-6335-4 (PDF) ISBN 978-951-39-6334-7 (nid.) ISSN 1456-9701 Copyright © 2015, by University of Jyväskylä Jyväskylä University Printing House, Jyväskylä 2015

ABSTRACT Meriläinen, Leena Characterization and immunological aspects of Borrelia burgdorferi pleomorphic round bodies. Jyväskylä: University of Jyväskylä, 2015, 64 p. (Jyväskylä Studies in Biological and Environmental Science ISSN 1456-9701; 307) ISBN 978-951-39-6334-7 (nid.) ISBN 978-951-39-6335-4 (PDF) Yhteenveto: Borrelia burgdorfin pleomorfisten muotojen karakterisointi ja immunologinen merkitys Diss. Borrelia burgdorferi sensu lato–bacteria causes the most common tick-borne infection, Lyme disease. B. burgdorferi is pleomorphic and can change the morphology dramatically as a response to environmental conditions to avoid immune response of the host or to promote adherence and dissemination in the host. The role of these pleomorphic variants in Lyme disease pathogenesis has been unclear and debated. This thesis focused on the characterization and immune reactions initiated by spherical round body forms (RBs) of B. burgdorferi. The aim was to study induction, cell envelope morphology and components, bioactivity, and phagocytosis of RBs. In addition, the immune response stimulated by RBs was analyzed in vitro and the suitability of RBs as a candidate for Lyme disease diagnosis was evaluated. Different culturing condition such as the presence of human serum induced pleomorphic forms. RBs displayed low metabolic activity; however, they were able to revert back to parental spirochetes. The analysis of the outer envelope revealed that RBs are not cell wall deficient as previously suggested, and they have different biochemical signature compared to spirochetes. We also presented the different protein expression between the RBs and spirochetes. Interestingly, results provided evidence that RBs are phagocytosed and processed differently in macrophages. Furthermore, RBs stimulated higher production of MCP-1 chemokine and diminished the production of IL-1β, IL-1ra, IL-6, MIF, MIP-1β and RANTES when compared to spirochetes. The immune response seen in Lyme disease patients was stronger