# Tick Immune Signaling, Microbiota, and Acquisition of Borrelia burgdorferi and Anaplasma phagocytophilum

> **NIH NIH P01** · UNIV OF MARYLAND, COLLEGE PARK · 2022 · $1,537,478

## Abstract

OVERALL - Abstract
The proposed Program Project (P01), entitled “Tick Immune Signaling, Microbiota, and Acquisition of
Borrelia burgdorferi and Anaplasma phagocytophilum” aims to understand the molecular mechanisms by
which the Ixodes tick immune system recognizes invading microbes, interfaces with resident gut microbiota,
and impact pathogen persistence. We discovered two unorthodox tick immune cascades that are (a) involved
in microbial recognition by an indirect “cross-kingdom” circuit triggered by a mammalian cytokine acquired in
the vector blood meal, or (b) by a direct induction by specific bacterial lipids through an atypical
immunodeficiency pathway. We also established that (c) interactions between tick gut microbiota and invading
pathogens shape vector physiology and immunity, ultimately impacting the ability of ticks to acquire B.
burgdorferi or A. phagocytophilum. Building on these paradigms and by combining the expertise and resources
from four institutions with impressive history of research involving tick-borne infections, we will determine how
discrete Ixodes tick immune pathways, either independently or synergistically, influence the entry and
persistence of two major pathogens, B. burgdorferi and A. phagocytophilum. These microbes constitute the
focus of our proposal due to their diverse structural and genetic features, their different lifestyles - either
extracellular or intracellular - and the fact that they are responsible for the most prevalent tick-borne infections
in the United States and many parts of Europe. This Program Project Grant leverages specific assays, tools
and methodologies developed by our laboratories, who have a long history of productive collaboration, and
which will be supported by an Administrative Core, and a Tick Resource Core whereby organisms and cell
lines will be shared. The proposed aims to achieve the goals of this P01 are 1) Develop a Tick Core that
provides the research reagents to all projects and to scientific community; 2) Determine how mammalian
factors present in tick blood meal stimulate multiple cross-species immunity signaling pathways impacting
persistence of diverse pathogens; 3) Investigate molecular basis of microbial detection in ticks via signaling
relays and crosstalk by multiple immune pathways; 4) Examine interactions between tick immunome and gut
microbiota and how these events impact persistence of tick-borne pathogens. Altogether, this proposal will
increase our fundamental understanding of how tick immune signaling pathways operate and interface with the
gut microbiota to influence the ability of diverse tick-borne pathogens to persist in the vector and subsequently
infect the vertebrate host. The outreach activities generated by sharing the research data, and resources to
the scientific community will plant new seeds of innovative research furthering our knowledge of tick-borne
infections. Finally, with the technical and conceptual breakthroughs expected, the P01 will enti...

## Key facts

- **NIH application ID:** 10440404
- **Project number:** 5P01AI138949-05
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Erol Fikrig
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,537,478
- **Award type:** 5
- **Project period:** 2018-07-13 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440404

## Citation

> US National Institutes of Health, RePORTER application 10440404, Tick Immune Signaling, Microbiota, and Acquisition of Borrelia burgdorferi and Anaplasma phagocytophilum (5P01AI138949-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10440404. Licensed CC0.

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