# Microbial Detection by Ixodes Scapularis Ticks

> **NIH NIH P01** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $386,250

## Abstract

PROJECT 2: Microbial Detection by Ixodes scapularis Ticks
Abstract: The Ixodes scapularis immune deficiency (IMD) pathway resembles the tumor necrosis factor
receptor network in mammals and elicits a humoral response against the spirochete Borrelia burgdorferi and
the rickettsial agent Anaplasma phagocytophilum – two distinct bacteria that cause Lyme disease and human
granulocytic anaplasmosis, respectively. The Pedra laboratory recently proposed the existence of a
functionally divergent IMD signaling cascade in ticks. We showed that the tick IMD network was activated in
response to the lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), a component of bacterial
inner membranes. Signaling relay in I. scapularis occurred in the absence of transmembrane peptidoglycan
recognition proteins (PGRPs), Fas-associated protein with a death domain (FADD) and IMD, the adaptor
molecule for which the immunological circuit was named. Interestingly, biochemical interactions proceeded
between x-linked inhibitor of apoptosis protein (XIAP), an E3 ubiquitin ligase, and the E2 conjugating enzyme
Bendless. For Project #2 in this P01 application, our central hypothesis states that the I. scapularis IMD
pathway functions as a molecular rheostat impacting acquisition and persistence of B. burgdorferi and A.
phagocytophilum. Aim#1 of this proposal will characterize the I. scapularis IMD pathway during pathogen
infection. Aim#2 of this proposal will define a molecular crosstalk between the I. scapularis IMD signaling
cascade and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway, as there is
increasing evidence that B. burgdorferi and A. phagocytophilum may be recognized by multiple pattern
recognition receptors. Collectively, our findings will enable the detection of novel signaling hubs in tick-
pathogen interactions and develop innovative scientific paradigms in microbial pathogenesis and arthropod
immunity.

## Key facts

- **NIH application ID:** 9976335
- **Project number:** 5P01AI138949-03
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Joao Pedra
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $386,250
- **Award type:** 5
- **Project period:** 2018-07-13 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976335

## Citation

> US National Institutes of Health, RePORTER application 9976335, Microbial Detection by Ixodes Scapularis Ticks (5P01AI138949-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976335. Licensed CC0.

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