# The Tick Immune Response During Microbial Infection

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $648,898

## Abstract

The tick Ixodes scapularis transmits several pathogens of relevance to public health,
including Borrelia burgdorferi (Lyme disease), Anaplasma phagocytophilum (human granulocytic
anaplasmosis), B. miyamotoi (tick-borne relapsing fever), Babesia microti (babesiosis) and Powassan virus
(tick-borne encephalitis). To date, while diverse areas of immunity have been studied in insects, the
underpinnings of the tick immune system are in its infancy, and the molecules involved in microbial sensing
remain chiefly undefined. Similarly, the molecular characterization of tick immune cells or hemocytes remains
mostly elusive. Over the previous funding period, we discovered a non-canonical immune deficiency (IMD)
network in I. scapularis and showed that the IMD pathway is important against B. burgdorferi and A.
phagocytophilum infection. Specifically, we uncovered the role of molecules that act on the I. scapularis IMD
pathway and provided mechanistic support for an observation that the immune system of ticks is fundamentally
different than insects. We made substantial progress in addressing the three specific aims, which resulted in
several peer-reviewed publications. For this R01 project (competing renewal), we will build on our earlier
findings and investigate the nexus between metabolism and immunology. Our central hypothesis states that
changes in metabolic status impact the immune system and microbial infection of ticks. Accordingly, in Aim #1
of this proposal, we will characterize the signaling flexibility of the IMD pathway in ticks. The classical textbook
definition of an immune pathway consists of a fixed stack of proteins that amplifies the immune signal from a
receptor to an effector. We will reveal that the tick IMD pathway is malleable and reprograms itself upon
metabolic changes and/or microbial infection. In Aim #2 of this grant application, we will categorize tick
hemocyte populations under distinct metabolic and microbial conditions through a platform that involves
coupling of single cell RNA sequencing (scRNA-seq) with a monoclonal antibody screening strategy. This
major resource to the vector biology community will show that metabolism and microbial infection affect tick
hemocyte biology. In Aim #3 of this submission, we will assess whether metabolism affects fitness parameters
associated with the life cycle of I. scapularis. We will also evaluate transstadial and transgenerational passage
of microbes in ticks. Altogether, this R01 project will demonstrate that bioenergetic processes likely define cost-effective
and/or energetically expensive tick-microbe interactions.

## Key facts

- **NIH application ID:** 10291359
- **Project number:** 2R01AI116523-06
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Joao Pedra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $648,898
- **Award type:** 2
- **Project period:** 2015-12-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10291359

## Citation

> US National Institutes of Health, RePORTER application 10291359, The Tick Immune Response During Microbial Infection (2R01AI116523-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10291359. Licensed CC0.

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