# Tick Saliva and Pathogen Transmission

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $555,415

## Abstract

Summary/Abstract: Ticks are hematophagous ectoparasites with worldwide public health and veterinary
importance. The success of their life strategy can be attributed, in part, to anti-inflammatory salivary proteins
that inhibit host immunity and facilitate pathogen transmission. As an example, we recently discovered a novel
mechanism of immune evasion by which the Ixodes scapularis salivary protein Sialostatin L2 inhibits activation
of the NLRC4 inflammasome. The NLRC4 inflammasome is a protein scaffold that regulates maturation of the
pro-inflammatory cytokines interleukin (IL)-1β and IL-18 through the enzyme caspase-1. We demonstrated that
Sialostatin L2 binds to the mammalian host protein Annexin A2. Upon infection with the rickettsial pathogen
Anaplasma phagocytophilum, Sialostatin L2 impairs assembly of the NLRC4 inflammasome. How tick effector
molecules, such as Sialostatin L2, are released during blood-feeding continues to be unknown. In what manner
pathogens, such as A. phagocytophilum, influence the delivery of tick molecules to the mammalian host remain
elusive. Whether the lymphatic system, a network of circulatory vessels, provides a rapid mechanism of
dissemination for immunological information during tick blood-feeding remains undetermined. Exosomes are
small extracellular vesicles that function in intercellular communication, facilitating host immune modulation.
For this R01 application, we show that I. scapularis exosomes interact with host immune cells and transport
anti-inflammatory tick salivary proteins. We report that A. phagocytophilum alters the oxidative state of
molecules within exosomes. Finally, we demonstrate that the lymphatic system acts as a conduit where the
release of tick proteins may affect inflammation. Accordingly, our central hypothesis states that the lymphatic
system plays a critical role in modulating inflammation during tick feeding; and that exosomes facilitate
intercommunication between I. scapularis and the mammalian host. Aim#1 of this proposal will identify anti-
inflammatory molecules within tick exosomes. Aim#2 will define oxidative post-translational modifications within
tick exosomes. Aim#3 will evaluate the role of the lymphatic system during tick feeding. Altogether, this
research will determine how tick-derived exosomes transport salivary proteins; investigate the underlying
mechanisms by which the rickettsial pathogen A. phagocytophilum affects exosomes; and reveal whether the
lymphatic system carries tick-derived molecules. As ticks and other arthropods transmit many human
pathogens during feeding, solving this intriguing scientific question will provide critical insights to the vector
biology community.

## Key facts

- **NIH application ID:** 10394207
- **Project number:** 5R01AI134696-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Joao Pedra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $555,415
- **Award type:** 5
- **Project period:** 2018-05-09 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10394207

## Citation

> US National Institutes of Health, RePORTER application 10394207, Tick Saliva and Pathogen Transmission (5R01AI134696-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10394207. Licensed CC0.

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