Catherine Brissette, Ph.D., Associate Professor
Project: Bacterial and host factors in Lyme disease pathogenesis
Mentor: Catherine Brissette, Ph.D., Associate Professor
Location: Department of Biomedical Sciences, Neuroscience Building
Description: Lyme disease (LD) is caused by infection with the bacterial pathogen Borrelia burgdorferi (Bb) and is a prevalent and continually emerging vector-borne disease in the United States, Europe, and Asia. Disseminated infection can lead to pathologies affecting the joints, heart, and central nervous system (CNS). Despite antibiotic treatment, a proportion of patients continue to suffer from debilitating symptoms. The mechanisms of CNS as well as bacterial and host risk factors for these manifestations are poorly understood, largely due to the lack of a tractable laboratory model for the study of LD in the CNS.
The meninges serve as an interface between CNS and periphery. The outermost layer of the meninges, the dura mater, possesses fenestrated blood vessels, lymphatic drainage, and a high density of resident immune cells capable of supporting a robust immune response. We now show acute and persistent extravascular Bb colonization of the dura mater after both needle inoculation and tick transmission, accompanied by increases in expression of inflammatory cytokines; in addition, we observe a robust interferon (IFN) response in the dura mater comparable to that seen during murine Lyme arthritis. Dura colonization is associated with leukocyte infiltration and mild meningitis, indicating an inflammatory state in the meninges of Bb-infected mice. We also demonstrate an increase in IFN-stimulated genes in both the cortex and hippocampus of infected mice, despite a lack of detectable spirochetes in the brain parenchyma. A sterile IFN response in the absence of Bb is unique to the brain parenchyma and could provide insights into the mechanism of inflammatory CNS associated with this pathogen.
Our tractable model will allow us to directly assess potential risk factors leading to more severe inflammatory CNS involvement, as well as test potential interventions.
