Fig. 8: Schematic illustration of early vascular interactions of B. burgdorferi and the proposed mechanics of transcellular intravasation.

Intravasation represents a critical step in systemic dissemination of Bb. The preparation process preceding the traversal of the blood endothelium includes at least two stages. The first phase seemingly involves probing, low-surface-contact interactions with the vasculature, primarily targeting PCs. In the second phase, Bb establishes multiple contact points with both ECs and PCs, transitioning from an exploratory stage to stable adhesion. Bb tends to localize between ECs and PCs, likely disrupting their function in maintaining vascular integrity. The BM appears to be the primary anatomical barrier to Bb intravasation, as no instances of Bb breaching this barrier were observed in this study. Regardless of the approach angle, Bb ultimately aligns itself lengthwise with the lymphatic endothelium before initiating traversal of the barrier. In transcellular traversal, Bb is sequentially encased in membrane infoldings of ECs. The stationary, motile, and non-motile states of Bb²¹ likely play a key role in the formation of the membrane infoldings and embedding of Bb in the EC. In all stages, Bb remained separated from the cellular cytosol by the plasma membrane and reached the lumen of the lymphatic vessel enclosed in this tunnel-like structure. Interstitial space (IS), vascular lumen (L), basement membrane (BM), endothelial cell (EC), pericyte (PC). Created in BioRender. Strnad, M. (2025) https://BioRender.com/0b7pn5r.