Session Type: Poster Session A
Session Time: 9:00AM-11:00AM
Background/Purpose: Lyme Disease is caused by the spirochete Borrelia Burgdorferi (Bb). The infection often begins in the skin, following a tick bite, and spreads to the joints, heart, and other tissues. The pathogenesis of Lyme disease is multifactorial, involving both pathogen-derived factors that influence dissemination, and host factors that are responsible for the inflammation and modulation of infection. PGLYRP1, a member of the peptidoglycan recognition proteins, is a host immune factor associated with the innate immune response. PGLYRP1 has been linked to pro-inflammatory processes in many chronic inflammatory diseases. The goal of this study is to understand the function of PGLYRP1 in Lyme Borreliosis.
Methods: Flow cytometry and ELISA were used to characterize the ability of Bb to recognize PGLYRP1. Wild type (WT) and PGLYRP1 knockout (KO) BALB/C mice, 6-8 weeks old, were infected subcutaneously with 1×106 spirochetes. Pathogen burden was measured by qPCR in heart, joint, and skin tissues in WT and KO mice at 25 days post infection. Blood samples were collected in both groups of mice to determine antibody titers against Bb. Serum cytokine profile was assessed, using a mouse chemokine/cytokine array. Histopathology was used to evaluate the severity of inflammation in both heart and joint tissues.
Results: In vitro assays showed a concentration-dependent interaction between Bb and PGLYRP1. Infected KO mice had significantly higher pathogen burden in hearts and joints, but no difference in skin samples compared to WT mice. There was a significant reduction in Bb specific IgG titers in sera obtained from infected KO mice. Similar to overall IgG, levels of IgG1, IgG2a, IgG2b, and IgG3 against Bb were significantly lower in PGLYRP1 infected KO mice than in WT. Notable increases in pro-inflammatory cytokines IFN-y, CXCL-9, and CXCL-10 were observed in infected KO mice. There was no significant difference in arthritis and carditis severity in WT and KO mice.
Conclusion: These studies suggest that PGLYRP1 plays a role in the host modulation of Bb in the systemic phase of infection and immune response. This leads to a better understanding of the pathogenesis of Lyme Disease.
To cite this abstract in AMA style:Gupta A, Arora G, Rosen C, Cao Y, Cerny J, Booth C, Palm N, Ring A, Fikrig E. The Role of PGLYRP1 in the Pathogenesis of Lyme Disease [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/the-role-of-pglyrp1-in-the-pathogenesis-of-lyme-disease/. Accessed November 23, 2020.
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