Antibody responses to Mycoplasma pneumoniae: protecting against and triggering disease

Abstract

_Mycoplasma pneumoniae_ (_Mp_) is a major bacterial cause of community-acquired pneumonia (CAP) in children and is even becoming a more important pathogen since the introduction of the pneumococcal conjugate vaccine. In light of the global increase in antibiotic resistance of _Mp_, the main goal is to clarify the pathogenesis of this infection to better understand the need and efficacy of antimicrobial treatment for this CAP and to develop diagnostic and therapeutic strategies for _Mp_-associated disease. Vaccination may be a promising alternative to antibiotics. However, to develop optimal approaches to vaccination against _Mp_ it is critical to understand the immune mechanisms that may contribute to protection and/or immunopathology. The main objective of this thesis was to determine the role of antibodies to _Mp_ in respiratory tract carriage, pulmonary infection, and extrapulmonary nervous system disease (encephalitis and Guillain-Barré syndrome), where an antibody-mediated pathogenesis has been suggested. We demonstrated in this thesis that the infection-induced _Mp_-specific antibody response is essential to clear pulmonary _Mp_ infection, but has a limited effect on _Mp_ carriage in the URT. Our data indicate that the humoral response to _Mp_ derived glycolipids is redundant for pulmonary clearance of _Mp_. The hypothesis that the _Mp_-induced IgG response against the major myelin glycolipid galactocerebroside (GalC) response turns autoimmune is not only of importance to understand _Mp_-associated immune-mediated diseases as encephalitis and Guillain-Barré syndrome, but also to construct _Mp_-targeting vaccines, as based on these findings such vaccines may include _Mp_-derived protein antigens rather than lipids thereby avoiding the induction of potential autoimmune anti-glycolipid antibodies. Overall, the results in this thesis pave the way for improved d