Comparative analysis of skin immune responses to hematophagous arthropods

Summary: Abstract Body: As the outermost barrier facing the external environment, the skin is a potent primary line of defense that employs various strategies against a variety of environmental, microbial, and other biological insults. Importantly, the skin is the first mammalian organ encountered by vectors of human pathogens, providing an avenue for the transmission of vector-borne diseases. In the United States, ticks are the most abundantly encountered vector of human clinical importance. Ticks are hematophagous ectoparasites known for their distinct ability to remain undetected and attached to a host’s skin for days, employing a remarkable toolbox of host immunomodulatory strategies to promote successful blood feeding. Our work aims to utilize the biological arsenal utilized by these ancient arthropods to elucidate mammalian immune strategies that facilitate skin immune responses. By leveraging single-cell and spatial transcriptomics in conjunction with animal modeling, we aim to employ a cross-species comparative approach to elucidate species-specific and core immune responses to these salient vectors. Our work reveals differential innate immune responses to each tick bite, suggesting variance in the immune microenvironment generated by these arthropods. We observe conserved macrophage responses and prominent differences in the neutrophil recruitment to the different tick-skin interfaces throughout the duration of tick feeding. Importantly, our understanding of skin immune responses to tick infestation may provide insights into broader skin immune programs, in addition to shedding light on mechanisms that promote pathogen transmission and other diseases states associated with these vectors. Luisa M. Valencia¹, Camila Ferraz¹, Hanna Laukaitis-Yousey¹, Liron Marnin¹, Francy Cabrera Paz¹, Joao H. Pedra¹ 1. Microbiology and Immunology, University of Maryland Baltimore School of Medicine, Baltimore, MD, United States. Innate Immunity, Microbiology, and Microbiome