Adaptive immunity in murine Bartonella infection

Bartonella is a genus of facultative-intracellular bacteria causing a long-lasting intra-erythrocytic bacteremia
in their mammalian reservoir hosts. Clearance of the bacteremia has been described to be mediated by antibodies. The exact clearance mechanism, however, has not been investigated so far. In this work, several
aspects related to the immune response against Bartonella have been studied in more detail, with an emphasis on the host’s protective antibody response.
For the manuscript "Neutralizing antibodies protect against murine Bartonella infection by interfering with
erythrocyte adhesion", infection of mice with B. taylorii served as a model for the infection of the natural
reservoir host by Bartonella. Bacteremia clearance kinetics and antibody responses were investigated in
different murine knock-out models. The clearance was observed to be independent of the presence of the
complement or Fc-receptors. An in-vitro erythrocyte adhesion inhibition assay was established, which correlated with protection by an immune serum or antibody in vivo and lead to the conclusion that neutralizing
antibodies protect by interfering with the red blood cell attachment of the bacteria. We identified a so far
understudied virulence factor, a predicted autotransporter on the bacterial surface, as a target of the murine
antibody response and suggest that it plays a role in erythrocyte adhesion.
Further experiments investigating the role of T-cells in clearing the bacteremia showed that although the
cytolytic response is negligible, T-help is essential for mounting a protective antibody response and thus
clearance.
Some experiments concerning both, the antibody and the T-cell response upon infection, were additionally
performed using B. birtlesii as a mouse model for Bartonella infection and indicate that the observations
made with B. taylorii are not species specific but seem to be common for lineage 4, if not for all Bartonella
species.
In addition, the vertical transmission of B. taylorii was investigated. The bacterium could be transmitted
from mother to embryo before birth, however, only if the mother had a deficiency in the adaptive immune
system. Immunocompetent offspring cleared the bacteremia after birth, indicating that there is no state of
immunological tolerance induced by transplacental transmission of Bartonella.