Antibody responses to Mycoplasma pneumoniae: protecting against and triggering disease
Antistoffen tegen Mycoplasma pneumoniae: beschermen tegen én veroorzaken ziekte
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 diagnostic and treatment strategies to reduce morbidity of pulmonary and/or extrapulmonary Mp disease and to tailor treatment to prevent the emergence of antibiotic resistance.