University of North Dakota School of Medicine and Health Sciences
Grand Forks, ND
Borrelia colonization of the dura mater induces inflammation in the CNS
Catherine (Cat) Brissette received her B.S. in Zoology from Louisiana State University, her M.S. with Dr. Paula Fives-Taylor at the University of Vermont, and her Ph.D. on interactions of oral spirochetes with the gingival epithelium from the University of Washington with Dr. Sheila Lukehart. She continued work with spirochetes as a postdoc with Dr. Brian Stevenson at the University of Kentucky, with a focus on outer surface adhesins and regulation of virulence factors in the Lyme disease spirochete Borrelia burgdorferi. Cat is now an Associate Professor at the University of North Dakota School of Medicine and Health Sciences where she continues work with pathogenic Borrelia species. Cat’s lab is broadly interested in bacterial-host interactions, and is particularly interested in those bacterial and host factors that impact colonization and immune responses in the central nervous system during infection with Lyme and relapsing fever spirochetes.
Conference Lecture Summary
Lyme disease, which is caused by infection with Borrelia burgdorferi, can lead to inflammatory pathologies affecting the joints, heart, and nervous systems including the central nervous system (CNS). Laboratory mice have been used to define the kinetics of B. burgdorferi infection and host immune responses in other tissues, but similar studies are lacking for the CNS of these animals. Previously, we reported the ability of B. burgdorferi to colonize the dura mater of mice during late disseminated infection. We now show acute and persistent extravascular B. burgdorferi colonization of the dura mater after both needle inoculation and tick transmission, accompanied by increases in expression of inflammatory cytokines. These increases in inflammatory gene expression are similar to what is observed with B. burgdorferi stimulation of human astrocytes, microglia, brain endothelial cells, and choroid plexus epithelial cells in vitro. In addition, we observe a robust interferon response in the dura mater. Dura colonization is associated with perivascular leukocyte infiltration and meningitis, demonstrating for the first time that B. burgdorferi-infected mice can develop meningitis. We also observe an increase in interferon-stimulated genes in both the cortex and hippocampus of infected mice, despite a lack of detectable bacteria in the brain parenchyma. Combined with the increases in inflammatory gene expression and downregulation of genes involved in maintenance of blood-brain and blood-CSF barriers in both mice and human cell culture models, these results could provide insights into the mechanism of B. burgdorferi dissemination into the CNS and the damage associated with this pathogen.