Characterization of spatial lipidomic signatures in tick-bitten guinea pig skin as a model for host-vector-pathogen interaction profiling.

Spatially aware de novo discovery methods are essential tools for therapeutic target identification in complex interphylum interactions such as arthropods and mammals. Notably, the methods should ideally be species agnostic, showing unique features of all interacting species. We evaluated the possibilities for matrix-assisted desorption/ionization mass spectrometry imaging (MALDI-MSI, referred to here as MSI) as a spatial "omics" method to simultaneously profile both an arthropod vector ( Ixodes tick) and a mammalian skin (guinea pig) in a bite model. We demonstrated the feasibility of MSI using gelatin-stabilized sample mounting that allowed for serial sectioning and mapping lipids in control and bitten skin, including the tick body and embedded mouthparts. We identified unique lipid ion patterns and observed lipid reorganization beneath the bite site consistent with histological changes. Furthermore, several ions were observed in the tick body with lower intensity in the dermis and control skin, suggesting the transmission of lipids from the tick to mammalian skin. These results establish a multi-system approach for discovering cross-species molecular interactions that can be further developed as targets to disrupt the vector-host interface.IMPORTANCEHere, we demonstrate the adaptability of spatial "omics" methods to identify interphylum processes regulated at the vector-host interface of ticks during a mammalian blood meal. This approach enables a better understanding of complex bipartite or tripartite molecular interactions between hosts, arthropod vectors and transmitted pathogens, and contributes toward the development of spatially aware therapeutic target discovery and description.