# Pathogenesis of Borrelia miyamotoi infection and Lyme coinfection in mice

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $418,750

## Abstract

PROJECT SUMMARY
Borrelia miyamotoi is a newly emerging relapsing fever (RF) spirochete transmitted by Ixodes tick spp that also
transmit the Lyme disease agent Borrelia burgdorferi. B. miyamotoi has recently been found to cause human
disease in areas where Lyme disease is endemic. Our group has isolated B. miyamotoi from a person with
disseminated Lyme disease, demonstrating that coinfection of B. miyamotoi and B. burgdorferi is occurring.
The full spectrum of B. miyamotoi-associated disease is not known, however other RF Borrelia cause blood
disorders, multiorgan system dysfunction, and fetal demise in humans. This project will use a mouse model to
define B. miyamotoi pathogenesis, host immune responses and risk factors for disease, and to examine the
impact of B. miyamotoi/B. burgdorferi coinfection on disease associated with each of these pathogens. Studies
will be conducted with our clinical isolate of I. scapularis-borne B. miyamotoi from Connecticut and a newly
generated tick isolate from Wisconsin. The duration of tick attachment for B. miyamotoi transmission will be
determined as well as kinetics of bacteremia, spectrum of disease and sites of persistence. As the greatest B.
miyamotoi diversity is seen among isolates from different Ixodes spp, we will evaluate disease expression after
infection with an I. pacificus-borne B. miyamotoi isolate. Studies in immunodeficient mice and mice with
altered immunity due to splenectomy, immunosuppressive agents, and pregnancy will be conducted to
delineate risk factors for more severe disease and adverse maternal-fetal outcomes. Based on preliminary
data, we hypothesize that the early innate defense against B. miyamotoi may differ from other RF Borrelia. We
will employ the advanced technology of cytokine time-of-flight mass spectrometry (CyTOF) to broadly
immunophenotype responding cells and the cytokines they produce during infection. We will determine
whether antibodies elicited by infection can prevent challenge infection in a naïve host or in the same host
challenged with tick-transmitted spirochetes. We will assess the impact of B. burgdorferi/B. miyamotoi
coinfection on disease expression associated with each of these pathogens. CyTOF will be conducted to
phenotypically and functionally characterize the host immune response to coinfection with B. miyamotoi and B.
burgdorferi, pathogens that thrive differentially in blood and connective tissue. The results of these studies will
provide clinically useful information regarding tick transmission dynamics, B. miyamotoi tissue tropism and
disease, and immune correlates of protection to predict risk factors for human disease and adverse outcomes.
!

## Key facts

- **NIH application ID:** 10059164
- **Project number:** 5R01AI130068-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Linda K. Bockenstedt
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2017-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10059164

## Citation

> US National Institutes of Health, RePORTER application 10059164, Pathogenesis of Borrelia miyamotoi infection and Lyme coinfection in mice (5R01AI130068-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10059164. Licensed CC0.

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