Klemen Strle, PhD

BIO

My laboratory conducts translational research in human immunology with a focus on Lyme disease and other tick-borne infections. Lyme disease presents with a range of manifestations which vary in severity and duration including complications that persist despite antibiotic therapy for the infection. The causes for this clinical heterogeneity are not well understood, and biomarkers to identify patients at greater risk for adverse outcomes are lacking. Our work is centered on elucidating mechanisms that lead to protective or pathogenic immune responses and how such responses are shaped by host and microbial (Borrelia burgdorferi) genetic factors.

In previous studies we used targeted approaches to identify specific host factors (SNPs) associated with excessive inflammation, more symptomatic early infection, and greater risk for antibiotic-refractory Lyme arthritis, a post-antibiotic complication of the disease. We then showed that these genetic factors are implicated in more severe disease because they set the stage for dysregulated Th1 and Th17 immune responses and autoreactive T and B cell immunity. Collectively, these studies demonstrated that adverse clinical outcomes in Lyme disease, including post-Lyme sequela, result at least in part from inappropriate immune responses involving microbial and host genetics. However, our knowledge of host and microbial determinants in Lyme disease remains limited.

In current work we are using targeted and discovery-based approaches to delineate the host genes and immune mechanisms underlying persistent symptoms following Lyme disease (PTLDS). These aspects of Lyme disease require the study of human patients and we have developed an integrative approach in human disease using Borrelia isolates, clinical information, and tissue from well-defined patients with a range of disease severity, coupled with functional studies in cell culture. We think that this approach effectively bridges mechanistic findings in vitro with clinically-relevant processes in human disease, and is more likely to provide useful information for diagnosis and treatment of Lyme disease and post-Lyme symptoms.