VCOM Research Day Program Book 2023

Graduate Student Research Biomedical

Juselyn D. Tupik 1 ; Mecaila E. McClune 2 ; Hailey W. Camp 1 ; Julia A. Gregory 1 ; Jules M. Dressler 2 ; Justin W. Markov Madanick 1 ; Margaret A. Nagai-Singer 1 ; Brandon L. Jutras 2 ; Irving C. Allen 1,3 Corresponding author: 1 Dept of Biomedical & Veterinary Sciences and 2 Dept of Biochemistry, Virginia-Maryland College of Veterinary Medicine, Virginia Tech; 3 Dept of Basic Science Education, Virginia Tech Carilion School of Medicine 06 Upping the “Anti” For Arthritis: Antimicrobial Defenses by Anti-Inflammatory Receptor NLRX1 During Lyme Disease

(WT) mice compared to knockouts, modulating bacterial load in vivo . We next determined in Nlrx1 - /- murine macrophages that NLRX1 may control infection by promoting Reactive Oxygen Species (ROS) mediated-cell death and autophagy, while decreasing cell proliferation and metabolic function. Finally, by infecting novel NLRX1 overexpression human monocytes, we found that elevated NLRX1 significantly decreased pro-inflammatory NF-κB mediated cytokine secretion. Ultimately, these results indicate that NLRX1 plays a protective role in mitigating Lyme arthritis in both murine and human models. Further, this protection may occur through NLRX1’s modulation of antimicrobial mechanisms and attenuation of NF-κB inflammatory signaling. Consequently, these promising results warrant further exploration of B. burgdorferi regulation by NLRX1 for development of new treatments for Lyme arthritis

Lyme disease, caused by the bacterium Borrelia burgdorferi , is a prevalent enigmatic and emerging infectious disease. Of the estimated 475,000 cases per year nationwide, 10-30% of patients will develop inflammation of the joints termed Lyme arthritis. This lifelong condition results from the overactivation of sustained pro-inflammatory innate immune signaling. Currently, there are limited therapeutics for antibiotic refractory Lyme arthritis, warranting investigation into how our innate immune system can mitigate this inflammation. Here, we studied how the anti inflammatory innate immune receptor NLRX1 could play a role in controlling B. burgdorferi infection. Because NLRX1 modulates inflammatory signaling, cell death, autophagy, and cell metabolism by associating with the mitochondria, we hypothesized that NLRX1 could have antimicrobial effects against Lyme disease and decrease arthritis presentation. Using novel Nlrx1 -/- mice, we found that NLRX1 significantly decreased arthritis severity in wildtype


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