Ph.D. Defense by Mads Lausen Nielsen
Mads Lausen Nielsen will defend his Ph.D. thesis "The role of the complement system in the defense against Chlamydia”
27.11.2020 kl. 13.00 - 16.00
13.00 Opening by the Moderator Svend Birkelund
13.05 PhD lecture by Mads Lausen Nielsen
14.00 Questions and comments from the Committee
Questions and comments from the audience at the Moderator’s discretion
16.00 Conclusion of the session by the Moderator
The Faculty Council has appointed the following adjudication committee to evaluate the thesis and the associated lecture:
Professor Andreas Klos, Medical School Hannover, Germany
Professor Christine Skerka, Hans Knöll Institute, Germany
Professor Jacek Lichota, Aalborg University, Denmark
Professor Svend Birkelund, Aalborg University, Denmark
Chlamydiae are highly successful human pathogens that cause frequent, long-lasting and recurrent infections. Chlamydial infections in humans are predominantly caused by the two species Chlamydia pneumoniae (C. pneumoniae) and Chlamydia trachomatis (C. trachomatis). C. pneumoniae causes upper and lower respiratory tract infections and accounts for approximately 10% of all community-acquired pneumonias. C. trachomatis is the leading cause of sexually transmitted bacterial infections and infects more than 120 million people globally each year. C. trachomatis causes chronic infections that over time induce severe tissue damage in the female genital tract that can lead to reproductive complications such as ectopic pregnancy and infertility. The only way to efficiently control Chlamydia infections and prevent serious infection-related sequelae is through vaccination. At present, the exact immunological mechanisms that provide protective immunity against Chlamydia are not fully understood and hence, the immunological goals for vaccination strategies are uncertain, which has seriously hampered chlamydial vaccine development. Evidence from animal studies suggest that the complement system may be actively involved in protective adaptive immune responses against chlamydial organisms, but may also be involved in Chlamydia-induced immunopathology. However, the role of complement in Chlamydia infections in humans is elusive.
In this dissertation, activation and deposition of human complement proteins were studied on the surface of different Chlamydia species and it was investigated how complement proteins affect the interaction between Chlamydia and primary human immune cells.
The findings presented in this dissertation contribute to our current understanding of the role of the complement system in Chlamydia infections in multiple ways. First, by providing visual and mechanistic evidence for the dispensable role of terminal complement complex formation in C. trachomatis neutralization assays reported in previous in vitro studies. Second, by identifying deposition of complement regulatory proteins not previously described for Chlamydia. Third, by demonstrating that complement-mediated opsonophagocytosis of Chlamydia by human phagocytes efficiently control Chlamydia infection in vitro. Fourth, by identifying bioactive cleavage fragments of complement C3 on the chlamydial surface using a novel mass spectrometry-based methodology. Finally, it was demonstrated that complement opsonization facilitates chlamydial recognition by human B-cells demonstrating the ability of the complement system to bridge innate and adaptive immune responses during chlamydial infections. However, the conceptualization of complement-driven adaptive immunity is still in its infancy, but, hopefully, this dissertation will encourage researchers to look deeper into this exciting area of anti-chlamydial immunity.
Department of Health Science and Technology
Ph.D. Defense take place via Zoom. A Zoom link will be sent to registered attendees prior to the defense via an Outlook invitation.
20.11.2020 kl. 12.00