Investigating the Human Immune Response to Ixodes scapularis Tick Bites

National Institute Of Allergy And Infectious Diseases

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Abstract

Tick-borne diseases (TBDs) pose a significant public health threat in the United States. The deer tick (Ixodes scapularis) transmits at least seven pathogens that cause human diseases, including Lyme disease, anaplasmosis, babesiosis, Borrelia miyamotoi disease, ehrlichiosis, and tick-borne encephalitis (deer tick virus/Powassan virus). Lyme disease is the most common, accounting for over 80% of tick-borne disease cases, with an estimated 476,000 cases diagnosed and treated annually in the US. Ticks are blood-feeding arthropods that need a blood meal at every active life stage. To feed, an ixodid tick must attach to a vertebrate host's skin and feed over several days. Tick saliva contains various proteins that help with feeding and pathogen transmission by preventing blood clotting, inhibiting platelets, dilating blood vessels, and modulating the immune response. Some animals, like rabbits and guinea pigs, develop an immune response against tick salivary proteins after repeated infestations, leading to tick rejection and protection against diseases like Lyme disease. Most people do not feel tick bites as they don't typically cause immediate irritation. However, repeated exposure can lead to sensitization and a protective immune response against Lyme disease. The specifics of this immune response are not well understood. Our team is studying the human immune response to tick bites in a controlled clinical setting to uncover key aspects of the innate and adaptive immune responses in the skin and blood after exposure to uninfected Ixodes scapularis ticks. We are also monitoring the development of tick-associated skin immunity, including itching. This research aims to identify tick salivary proteins that could serve as targets for an anti-tick vaccine. In the past year, we expanded the study to include single-cell analysis. We optimized a protocol for preparing high-quality skin cell suspensions for single-cell RNA sequencing (scRNA-seq) analysis of human skin. We also processed and preserved skin biopsies for histopathology and spatial analysis. We plan to use CosMx technology by Nanostring for single-cell spatial gene analysis, which will provide insights into the biological processes involved in the host response. Additionally, ticks fed on participants are being collected for RNA and protein extraction for transcriptomic and proteomic analysis.