# Functional Impact of Stress Granules on Tick-Microbe Interactions

> **NIH NIH R21** · WASHINGTON STATE UNIVERSITY · 2021 · $198,798

## Abstract

Abstract
Arthropod immunity is a key factor influencing vector competence. We recently identified an atypical Immune
Deficiency (IMD) pathway in Ixodes scapularis ticks that responds to and restricts Borrelia burgdorferi (Lyme
disease) and Anaplasma phagocytophilum (Human Granulocytic Anaplasmosis). Host cell stress-responses are
closely intertwined with immunity and can function to either potentiate or antagonize immune signaling. Whether
stress-response pathways intersect with arthropod immunity to influence vector competence remains unknown.
Stress Granules (SGs) are aggregates of RNA and protein that transiently form in the cytoplasm of stressed
cells, such as during infection. SG formation is highly conserved throughout eukaryotes and has known immune
regulatory roles in mammals. Once formed, SGs become cell signaling hubs that can intercept molecules from
other pathways to modulate cellular processes. For instance, SGs can inhibit the mammalian analogue to the
IMD pathway, the Tumor Necrosis Factor Receptor (TNFR) network, by sequestering signaling proteins away
from immune complexes. SGs are induced when eIF2α (eukaryotic translation initiation factor 2α) is
phosphorylated by stress-sensing kinases, such as PERK (protein kinase R-like endoplasmic reticulum kinase).
In this R21 application, we report that PERK-eIF2α signaling promotes A. phagocytophilum colonization and
replication in tick cells. This observation together with known immune inhibitory roles of eIF2α-induced SGs
prompted us to look for SG formation in ticks. We found 13 SG-assembly genes that are induced in the salivary
glands and/or midguts of A. phagocytophilum-infected ticks. Accordingly, our central hypothesis is that PERK-
eIF2α-induced SGs antagonize immune signaling in ticks, which promotes bacterial pathogen colonization.
AIM 1 of this proposal will evaluate whether bacterial infection induces SGs in tick cells using immunofluorescent
microscopy, protein biochemistry and pharmacological inhibition. AIM 2 will assess the impact of SGs on
bacterial colonization and tick immunity in vitro using transcriptional knockdown and pharmacological
modulators. AIM 3 will investigate whether SG machinery influences pathogen colonization and maintenance in
vivo by using transcriptional knockdown in larvae followed by A. phagocytophilum or B. burgdorferi challenge.
As SG formation is a conserved evolutionary mechanism, investigating this phenomenon as it relates to
arthropod immunity and vector competence will provide novel insights for the broader vector biology community.

## Key facts

- **NIH application ID:** 10187515
- **Project number:** 5R21AI148578-02
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Dana Kathleen Shaw
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $198,798
- **Award type:** 5
- **Project period:** 2020-06-09 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10187515

## Citation

> US National Institutes of Health, RePORTER application 10187515, Functional Impact of Stress Granules on Tick-Microbe Interactions (5R21AI148578-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10187515. Licensed CC0.

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