# Neutrophil-Mediated Bacterial Dissemination and Host Immunopathogenesis in a Murine Scrub Typhus Model

> **NIH NIH R21** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2020 · $237,000

## Abstract

Abstract
Scrub typhus is a life-threatening zoonosis caused by Orientia tsutsugamushi organisms that are transmitted
by the larvae of trombiculid mites. About one third of the world’s population is at risk of infection. However, the
mechanism of bacterial dissemination from the skin and the reason that innate immune cells fail to control local
infection are unknown; it is technically challenging to track the bacteria during infection in vivo. This project will
use our newly established intradermal (i.d.) infection mouse model and fluorescence-labeled bacteria to define
the mechanisms of bacterial dissemination. Our preliminary mouse data revealed containment and survival of
CFSE-labeled Orientia in neutrophils for at least 12 hours in vitro. We also found neutrophils as the major
infiltrating cell population responding to inactivated Orientia in the mouse skin. Given that neutrophil depletion
via antibodies promoted mouse survival against acute infection in a lethal infection (i.v. infection model), we
want to test the hypothesis that Orientia bacteria can hijack and utilize neutrophils as Trojan horses against
host bactericidal activities, allowing bacterial dissemination from the initial skin infection sites to visceral organs.
Specific Aim 1 will examine the dynamics of myeloid cell recruitment in the skin and the bacterial load in unique
cell populations using multi-color flow cytometry. We will also evaluate effects of Orientia infection on
neutrophil bactericidal activity, including reactive oxygen species generation, neutrophil extracellular trap
formation, and granules/cytokine production both in vitro and in vivo. Specific Aim 2 will define neutrophil-
mediated Orientia dissemination and immunopathogenesis. We will track CFSE-labeled Orientia among
various organs (e.g. draining lymph nodes, bone marrow, lung, and spleen) after i.d. inoculation. Cellular
markers of reverse migration will also be examined. To further validate the pathogenic role of neutrophils
during disease progression, we will modulate neutrophils migration using selective and potent antagonists.
This work will provide new insights into the innate immune determinants of Orientia infection and will lay the
groundwork for our long-term goal of developing promising therapeutic strategies for this and other vector-
borne diseases that share a common route of pathogen dissemination.

## Key facts

- **NIH application ID:** 10039314
- **Project number:** 1R21AI153586-01
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Yuejin Liang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $237,000
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10039314

## Citation

> US National Institutes of Health, RePORTER application 10039314, Neutrophil-Mediated Bacterial Dissemination and Host Immunopathogenesis in a Murine Scrub Typhus Model (1R21AI153586-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10039314. Licensed CC0.

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