# Cross-Species Immunity Signals Impacting Persistence of Tick-Borne Pathogens

> **NIH NIH P01** · UNIV OF MARYLAND, COLLEGE PARK · 2022 · $386,250

## Abstract

PROJECT 1
Abstract
Despite increasing recognition of tick as a highly efficient disease vector, our knowledge of its immune system,
especially how the vector recognizes and mounts antimicrobial responses to invading pathogens has been
very limited. Recently, we discovered a novel cross-species signaling cascade that allows Ixodes scapularis
tick to sense a specific mammalian factor present in the infected blood meal as an infection cue, triggering a
potent microbicidal response that limits the proliferation of invading pathogens like Borrelia burgdorferi. These
studies also uncovered a critical role of a tick “immune” GTPase, the Ixodes GTPase (IGTPase) in the tick gut,
that is induced by ingested mammalian IFNγ. The IFNγ, through downstream Ixodes STAT signaling events,
activates IGTPase to generate potent borreliocidal responses. In the current Project 1 of our Program Project
Grant (PPG), we propose to investigate the molecular details of how this interferon-like defense operates in
ticks. In our first series of experiments, we will systematically define how IFNγ induces the tick JAK/STAT
pathway, including its regulation of IGTPase. We will investigate how IGTPase-induced tick antimicrobial
proteins limit B. burgdorferi persistence in the vector. Besides, recent studies showed that arthropod immunity
is influenced by crosstalk between discrete signaling pathways, which may impact the persistence of
pathogens with overlapping range, such as B. burgdorferi and A. phagocytophilum. Therefore, our second
group of experiments will examine how IFNγ-like tick defense system impacts the persistence of additional
pathogens like Anaplasma phagocytophilum. We will also define the crosstalk between immune pathways,
which will synergize the studies proposed in other projects of our PPG - Project 2 for defining mechanistic
operation of the immune deficiency pathway (IMD) with other tick immune pathways, and the gut microbiota
which is the focus of Project 3. These mechanisms altogether ultimately govern the persistence of B.
burgdorferi and A. phagocytophilum. Overall, our study will shed new insight into the operation of cross-
species signaling mechanisms involving discrete or co-operative tick innate immune pathway(s) that influence
persistence of multiple tick-borne pathogens, including co-infection in ticks.

## Key facts

- **NIH application ID:** 10440407
- **Project number:** 5P01AI138949-05
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** UTPAL PAL
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,250
- **Award type:** 5
- **Project period:** 2018-07-13 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440407

## Citation

> US National Institutes of Health, RePORTER application 10440407, Cross-Species Immunity Signals Impacting Persistence of Tick-Borne Pathogens (5P01AI138949-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10440407. Licensed CC0.

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