Ixodes scapularis nymph saliva protein blocks host inflammation and complement-mediated killing of Lyme disease agent, Borrelia burgdorferi

• DOI: 10.3389/fcimb.2023.1253670
• Publication Date: 2023-10-27T02:24:16Z
• Authors: Emily Bencosme-Cu...; Tae Kwon Kim; Thu-Thuy Nguyen; Jacquie Berry; Jianrong Li; Leslie Garry Adams; Lindsey A. Smith; Syeda Areeha Batool; Daniel R. Swale; Stefan H. E. Kauf...; Yava Jones-Hall; Albert Mulenga
• Keywords: Ixodes scapularis

Tick serine protease inhibitors (serpins) play crucial roles in tick feeding and pathogen transmission. We demonstrate that Ixodes scapularis (Ixs) nymph saliva serpin (S) 41 (IxsS41), secreted by Borrelia burgdorferi (Bb)-infected ticks at high abundance, is involved regulating evasion of host innate immunity promoting colonization Bb. Recombinant (r) proteins were expressed Pichia pastoris, substrate hydrolysis assays used to determine. Ex vivo (complement hemostasis function related) (paw edema effect on Bb C3H/HeN mice organs) conducted validate function. rIxsS41 inhibits chymase cathepsin G, pro-inflammatory proteases are released mast cells neutrophils, the first immune site. Importantly, stoichiometry inhibition analysis revealed 2.2 2.8 molecules needed 100% inhibit 1 molecule respectively, suggesting findings here likely events Furthermore, chymase-mediated paw edema, induced cell degranulator, compound 48/80 (C48/80), was blocked rIxsS41. Likewise, reduced membrane attack complex (MAC) deposition via alternative lectin complement activation pathways dose-dependently protected from killing. Additionally, co-inoculating with together or a mixture (rIxsS41 C48/80). Findings this study suggest IxsS41 markedly contributes Therefore, we conclude potential candidate for an anti-tick vaccine prevent transmission Lyme disease agent.