# Understanding Human Immunological Responses to Ixodes Tick Bites

> **NIH NIH R21** · TUFTS UNIVERSITY BOSTON · 2020 · $247,500

## Abstract

ABSTRACT
Ixodes ticks are vectors of many important human diseases including but not limited to Lyme disease,
babesiosis, anaplasmosis, Borrelia miyamotoi disease, and tick-borne encephalitis causing viruses. Animals
fed on by ticks may develop resistance to repeated tick feedings and individual humans have shown differing
levels of resistance to tick feeding. While much has been learned about responses to ticks in model animals,
recent studies have shown that ticks alter their salivary content based on the host they are feeding on and that
immunological responses to tick bites can vary significantly between hosts. Human responses to tick bites
have not been studied systematically due to the difficulty in obtaining consistent, characterizable samples. Our
laboratories are involved in a multi-year study to examine the use of ticks as a device (xenodiagnosis) for
detecting the persistence of the Lyme disease causing organism, Borrelia burgdorferi, after antibiotic treatment
in patients. As a result, we have a large, well characterized collection of serum, plasma, whole blood and skin
biopsy samples from around tick bite sites. Here, in response to a specific RFA (PAR-18-860) to study the
Immune Response to Arthropod feeding, we propose to study human cellular and adaptive immune responses
to tick bites and attempt to correlate specific components of each with resistance to tick feeding. In Aim 1, we
will examine skin biopsy samples from patients where ticks fed either poorly or well to determine the cytokine
profile in response to the bite using RNAseq. We will also determine the histological characteristics of the
cellular infiltrate around the tick bite site. Using spatial transcriptomics, we will examine the cellular
transcriptome as it relates to the tick bite site and understand the contribution of different cell types to the
inflammatory milieu. In Aim 2, we will determine the impact of the adaptive immune response on tick feeding.
Using artificial feeding membranes, we will test serum from patients who experienced good and poor feeding
as well as the effects of the evolving immune response over time and after multiple exposures to ticks. At the
completion of this project, we will have established the human immune correlates of successful and
unsuccessful tick feeding which will form the building blocks for designing future approaches to preventing tick
borne diseases through interfering with tick feeding.

## Key facts

- **NIH application ID:** 9953965
- **Project number:** 5R21AI146841-02
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Linden T Hu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,500
- **Award type:** 5
- **Project period:** 2019-06-13 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9953965

## Citation

> US National Institutes of Health, RePORTER application 9953965, Understanding Human Immunological Responses to Ixodes Tick Bites (5R21AI146841-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9953965. Licensed CC0.

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