# Regulation of Skin Immunity by a Tick Bite

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $231,750

## Abstract

Summary/Abstract: Ticks transmit bacteria, viruses and parasites that cause disease in humans and other
animals. This phenomenon is partly due to the secretion of redundant and pluripotent salivary proteins that
disrupt host homeostasis and alter inflammation upon blood-feeding. Recently, extracellular vesicles, a
heterogenous population of nanovesicles that mediate interspecies communication, were shown to facilitate
pathogen transmission to mammals. We developed a tick salivary organoid system that mimics extracellular
vesicle release. We also manipulated the biogenesis of tick extracellular vesicles by silencing the expression
of N-ethylmaleimide-sensitive factor attachment receptor (SNARE) genes through RNA interference. Finally,
we provided causality to our findings by showing that tick extracellular vesicles affect resident dendritic
epidermal T cells (DETCs) in the skin. How immune cells are targeted by tick nanovesicles in the skin remains
unsettled. Whether tick extracellular vesicles have functional plasticity during interspecies relationships
remains elusive. In this R21 application, we will explore the central hypothesis that tick extracellular vesicles
provide an advantageous skin immune environment for Ixodes scapularis feeding via the DETC-keratinocyte
axis. DETCs interact with keratinocytes, which comprise approximately 95% of the skin epidermal layer. In Aim
#1 of this proposal, we will determine whether the effect of I. scapularis extracellular vesicles on DETCs is
direct or indirect. We will use single cell RNA sequencing coupled with animal models devoid of DETCs to
evaluate the directionality of the skin immune response during a tick bite. In Aim #2 of this grant proposal, we
will ascertain the architecture of the skin when the biogenesis of tick extracellular vesicles is disrupted. We will
measure the immune response of DETCs through skin biopsies via flow cytometry coupled with cell sorting,
microbial stimulation and spatial transcriptomics. Spatial transcriptomics combines traditional histology
information with single cell gene expression analysis and positional barcoding. Thus, we will construct an
architectural map of genes associated with DETCs and keratinocytes during a tick bite. Collectively, this R21
project will underscore the importance of ticks as arthropods of

## Key facts

- **NIH application ID:** 10337568
- **Project number:** 1R21AI165520-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Joao Pedra
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $231,750
- **Award type:** 1
- **Project period:** 2021-11-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337568

## Citation

> US National Institutes of Health, RePORTER application 10337568, Regulation of Skin Immunity by a Tick Bite (1R21AI165520-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10337568. Licensed CC0.

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