# Tick Saliva and Pathogen Transmission

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $669,936

## Abstract

Summary/Abstract: Ticks are ancient hematophagous arthropods that transmit pathogens of public health
and veterinary importance. During feeding, they disrupt host homeostasis through salivary molecules that
perturb inflammation, blood coagulation and nociception. For more than 100 years, tick saliva has fascinated
researchers with its anti-hemostatic, analgesic, and anti-inflammatory properties. Over the previous funding
period, we used orthogonal approaches and a cell-centric perspective to better understand the intricate biology
occurring between ticks and their hosts. We uncovered that tick extracellular vesicles (EVs) carry bioactive
molecules and mediate interspecies communication with mammals. We discovered that tick EVs affect
dendritic epidermal T cells (DETCs) and promote distinct outcomes of microbial transmission to mammals.
DETCs are a subset of murine γδ T cells located in the skin epidermis that have a critical role in wound healing.
DETCs interact with highly specialized epithelial cells (keratinocytes), which comprise approximately 95% of
the epidermal layer in the skin. Under homeostasis, epidermal cells differentiate and migrate to the skin
surface where they are shed while being replenished at the basal layer or stratum basale. Upon an injury,
wound healing occurs in four stages of tissue repair and replacement: hemostasis, inflammation, proliferation,
and remodeling. Unfortunately, the epidermis has been mostly neglected when studying the relationship
between ticks and their mammalian hosts. For the next iteration of this project (R01 competing renewal), we
will investigate the effect of tick EVs on the DETC-keratinocyte dialogue. We will also examine how tick EVs
affect the wound healing function of keratinocytes during feeding. Single-cell RNA sequencing, flow cytometry,
cell sorting, and murine genetics will be used to uncover how DETCs and keratinocytes communicate during
feeding of an ectoparasite. Lineage tracing combined with drug perturbations and allied with sophisticated
intravital imaging techniques will be used to track the proliferation, differentiation, and migration of epidermal
cells. Our central hypothesis states that tick EVs disrupt the dialogue occurring between DETCs and
keratinocytes during feeding altering epidermal wound healing. In Aim #1 of this proposal, we will investigate
the effect of tick EVs on the crosstalk between DETCs and keratinocytes. In Aim #2 of this grant application,
we will ascertain how tick EVs affect epidermal wound healing during a tick bite and microbial transmission.
Collectively, we will provide a distinct biological insight and fill a current gap in knowledge for ectoparasitology
and microbial diseases by describing how ticks affect the epidermal environment during feeding.

## Key facts

- **NIH application ID:** 10993827
- **Project number:** 2R01AI134696-06A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Joao Pedra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $669,936
- **Award type:** 2
- **Project period:** 2018-05-09 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10993827

## Citation

> US National Institutes of Health, RePORTER application 10993827, Tick Saliva and Pathogen Transmission (2R01AI134696-06A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10993827. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*