# Tick Gut Immunome- Gut Microbiota Interactions in the Context of Tick-Borne Pathogens

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

## Abstract

PROJECT 3 - Abstract
 This proposal will determine the influence of tick gut microbiota on tick gut immune
signaling pathways JAK/STAT and IMD and the functional consequence on Borrelia burgdorferi,
and Anaplasma phagocytophilum survival in the tick - an important determinant of infection
prevalence. Our earlier work (Narasimhan et al, Cell Host Microbe 15:58-71, 2014) and our recent work
(Abraham et al, Proc Natl Acad Sci,114: E781-790, 2017) demonstrate that tick gut microbiota modulates
B. burgdorferi colonization and A. phagocytophilum infection of Ixodes scapularis. Perturbation of the gut
microbiota (dysbiosis) disrupts the integrity of the peritrophic matrix - an acellular glycoprotein-rich layer
that separates the gut epithelium from the lumen. While B. burgdorferi resides on the gut epithelium and
an intact peritrophic matrix (PM) affords protection from toxic components in the tick gut enhancing their
colonization of the gut, A. phagocytophilum circumvents the PM barrier to infect the gut and finally the
salivary glands by as-yet-unknown mechanisms and exploits a compromised PM to efficiently breach the
PM barrier. These observations reveal a novel and apparently contrasting facet of Borrelia-tick and
Anaplasma-tick interactions. In a more recent effort (Narasimhan et al, Nat Commun. 184: s41467,
2017), we draw attention to the dynamic interactions of the tick microbiota with tick gut defense
responses and to the diverse ways in which tick microbiota might influence pathogen survival in the tick
gut. These findings, together with the observations of Projects 1 and 2 emphasize the influence of the
interactions between tick gut microbiota- and immune responses on pathogen survival in the tick.
 In Aim 1 we will characterize the extent to which gut microbiota interacts with tick gut immune
responses (specifically JAK/STAT and IMD) and host cytokines (specifically IFN) that enter the tick gut,
and define gut bacterial profiles that are significantly influenced by the tick and host immune responses
and vice-versa.
 In Aim 2 we will reconstitute specific gut microbiota or bacterial components and determine how
this influences tick gut immune signaling and ultimately the survival of B. burgdorferi or A.
phagocytophilum in the tick
 This research endeavor will unfold a mechanistic understanding of the functional consequence of
tick gut microbiota on tick gut immune signaling and the survival of two important tick-borne pathogens
that cause human disease.

## Key facts

- **NIH application ID:** 10440409
- **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:** $386,250
- **Award type:** 5
- **Project period:** 2018-07-13 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440409

## Citation

> US National Institutes of Health, RePORTER application 10440409, Tick Gut Immunome- Gut Microbiota Interactions in the Context of Tick-Borne Pathogens (5P01AI138949-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10440409. Licensed CC0.

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