Active Invasion of Porphyromonas gingivalis and Infection-Induced Complement Activation in ApoE-/- Mice Brains.

Periodontal disease is a polymicrobial inflammatory disease that leads to chronic
systemic inflammation and direct infiltration of bacteria/bacterial components,
which may contribute to the development of Alzheimer's disease. ApoE-/- mice were
orally infected (n = 12) with Porphyromonas gingivalis, Treponema denticola,
Tannerella forsythia, and Fusobacterium nucleatum as mono- and polymicrobial
infections. ApoE-/- mice were sacrificed following 12 and 24 weeks of chronic
infection. Bacterial genomic DNA was isolated from all brain tissues except for
the F. nucleatum mono-infected group. Polymerase chain reaction was performed
using universal 16 s rDNA primers and species-specific primer sets for each
organism to determine whether the infecting pathogens accessed the brain.
Sequencing amplification products confirmed the invasion of bacteria into the
brain during infection. The innate immune responses were detected using
antibodies against complement activation products of C3 convertase stage and the 
membrane attack complex. Molecular methods demonstrated that 6 out of 12 ApoE-/- 
mice brains contained P. gingivalis genomic DNA at 12 weeks (p = 0.006), and 9
out of 12 at 24 weeks of infection (p = 0.0001). Microglia in both infected and
control groups demonstrated strong intracellular labeling with C3 and C9, due to 
on-going biosynthesis. The pyramidal neurons of the hippocampus in 4 out of 12
infected mice brains demonstrated characteristic opsonization with C3 activation 
fragments (p = 0.032). These results show that the oral pathogen P. gingivalis
was able to access the ApoE-/- mice brain and thereby contributed to complement
activation with bystander neuronal injury.

No comments: