Upping the “Anti-” for arthritis: Antimicrobial defenses through anti-inflammatory NOD-like Receptor NLRX1 during Lyme disease

Abstract Lyme disease, caused by the bacterium Borrelia burgdorferi, is an emerging infectious disease of global concern. Roughly 60% untreated patients will develop synovitis joints termed arthritis, resulting from sustained cytokine and chemokine production innate immune system. Currently, there are limited therapeutics for antibiotic-refractory warranting investigation into how our system can mitigate this inflammation. Here, we studied anti-inflammatory NOD-like Receptor (NLR) NLRX1 could play a role in controlling infection. Because modulates inflammatory signaling, cell death, autophagy, metabolism, hypothesized that have unique antimicrobial effects against disease. Using novel Nlrx1 −/−mice, found significantly decreased arthritis severity wildtype mice compared to knockouts modulated bacterial load vivo. We next determined −/−murine BMDMs may control infection promoting Reactive Oxygen Species (ROS) mediated-cell death while decreasing proliferation modulating inflammasome activation vitro. Finally, infecting overexpression human monocytes, elevated pro-inflammatory NF-κB-mediated secretion. Ultimately, these results indicate plays protective mitigating murine models. Further, protection occur through NLRX1’s modulation attenuation NF-κB signaling. Consequently, warrant further exploration regulation development new treatments arthritis. Supported grants NIH/NIAID (R21AI159800) Cohen Foundation