Embedded Files
Host-Pathogen Interactions and Immunopathology During Lyme Disease
Host-Pathogen Interactions and Immunopathology During Lyme Disease
Lyme disease, caused by infection with the spirochete Borrelia burgdorferi, has an incidence approaching 500,000 cases resulting in total direct medical costs of ~$1 billion per year in the USA. Lyme disease is a multisystem disease that causes localized inflammatory pathologies including arthritis, carditis, and neurological complications. Neurologic disease, referred to as Lyme neuroborreliosis affects 10-20% of patients in the USA. Manifestations of neuroborreliosis can include meningitis, nerve dysfunction, and behavioral changes affecting mood, cognition, and sleep/fatigue. Further, up to 20% of patients that receive appropriate antibiotic treatment develop Post-Treatment Lyme Disease Syndrome, a condition of continuing symptoms after resolution of infection that may have an autoimmune component. The Casselli lab seeks to understand the tissue-specific mechanisms of bacterial invasion and infection-induced inflammation, with a focus on the central nervous system. Using a combination of bacterial genetics as well as in vitro and in vivo models of Lyme disease, the aims of the Casselli lab include:
1) Risk factor identification: Why do some patients develop Lyme neuroborreliosis while most do not?
2) Biomarker identification: There is an urgent need for a reliable non-invasive test for diagnosing neuroborreliosis.
3) Characterization of pathologic immune mechanisms relevant to Post-Treatment Lyme Disease Syndrome.
The overall goal of these aims is to identify factors that can be exploited to develop novel disease prevention and management strategies for neurologic Lyme disease. See below for our ongoing projects in the Casselli lab towards this goal, or check out a list of Dr. Casselli's publications.
Mechanisms of Acute Lyme Neuroborreliosis
Mechanisms of Acute Lyme Neuroborreliosis
Importantly, the ability of B. burgdorferi to colonize a particular tissue and the resulting inflammatory pathologies are dependent on specific interactions between the host and pathogen within the local microenvironment. Understanding the molecular mechanisms relevant to early central nervous system invasion is therefore essential for identifying risk factors for Lyme neuroborreliosis, and could reveal novel biomarkers and disease management strategies. Epidemiologic evidence suggests that some isolates of B. burgdorferi are more neuroinvasive than others. Genetic differences between B. burgdorferi strains cannot fully account for the observed heterogeneity in disease manifestations, suggesting host factors are also involved. The Casselli lab has successfully modelled this disease heterogeneity in laboratory models of Lyme neuroborreliosis, and is currently working to identify the specific bacterial and host factors that impact neuroinvasiveness and downstream inflammation during active B. burgdorferi infection.
Mechanisms of Antibiotic-Refractory Lyme Neuroborreliosis
Mechanisms of Antibiotic-Refractory Lyme Neuroborreliosis
Antibiotic-refractory Lyme arthritis is frequently accompanied by autoimmune responses against tissue repair proteins that accumulate in joint tissue during infection. Likewise, studies from the Casselli lab show localized vascular damage and disruption of processes involved in tissue repair in the meninges of B. burgdorferi-infected mice, which could have autoimmune consequences against proteins released in the damaged tissue. Tissue-specific inflammatory pathology is influenced by the local T cell response to B. burgdorferi in joints and heart tissue, however little is known about the role of local adaptive immune responses during neuroborreliosis. Using laboratory models of Post-Treatment Lyme Disease Syndrome, the Casselli lab is seeking to identify dysregulated cytokine responses as well as B. burgdorferi-derived antigens and host-derived autoantigens associated with meningeal pathology, with a focus on those overrepresented in other neurologic or autoimmune diseases.
Other Research Interests
Other Research Interests
In addition to questions about host-pathogen interactions in the context of mammalian infection, the Casselli lab is also interested in more basic molecular-focused projects on the biology of B. burgdorferi, including genome modification systems and mechanisms of gene expression regulation.
Page updated
Google Sites
Report abuse