# Host Response and Immunity to Yersenia pestis Infection

> **NIH NIH R01** · UNIVERSITY OF MISSOURI-COLUMBIA · 2021 · $365,222

## Abstract

PI: Anderson, Deborah M
 Project Summary
 
“Host response and immunity to Yersinia pestis infection”
Project Summary
 Type I interferons are expressed by eukaryotic cells upon intracellular invasion by microbial pathogens
and they induce a potent anti-viral response. Yet during bacterial infection, expression of type I IFN often
leads to a pathologic response that depletes populations of immune effector cells necessary to mediate
clearance. Our laboratory has shown that type I IFN signaling contributes to neutrophil depletion during
infection by Yersinia pestis, a Gram-negative bacterium that is the causative agent of the plague. Bubonic
plague is a highly infectious vector borne disease that can be transmitted through the respiratory route and
disseminated through the vasculature of its victims. Septicemic and pneumonic plagues involve the rapid
development of an uncontrolled systemic inflammatory response that causes the clinical collapse of the
patient, even with antibiotic treatment. These three forms of plague have been responsible for three major
pandemics and still cause annual cases of human disease with a high mortality rate worldwide including a
hotspot in the Southwestern United States. To date, little about the host responses that directly or indirectly
contribute to the progression of plague. Such responses may present new strategies to approach the post-
symptomatic treatment of plague and other acute inflammatory diseases. In this application, we propose to
study interactions between phagocytic cells and Y. pestis that are responsible for inducing inflammatory
responses that contribute to the progression of infection in a murine model. We have identified the broadly
conserved Toll-like receptor 7 (TLR7) as activated during infection by wild type Y. pestis. Activation of TLR7
by Y. pestis triggers a non-canonical signaling pathway that induces the expression of type I IFN and its
downstream IFN stimulated genes which subsequently interfere with the neutrophilic response and promote
the progression of disease. In this project, we aim to understand the molecular signaling events of this novel
pathway and their role during infection with Y. pestis. Our long term goal is to use the information gained from
this program to better understand innate immune response to bacterial infection and develop host-targeted
therapeutics that broadly protect from acutely inflammatory infectious diseases such as the infamous
pneumonic plague.

## Key facts

- **NIH application ID:** 10142355
- **Project number:** 5R01AI129996-05
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** DEBORAH M ANDERSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $365,222
- **Award type:** 5
- **Project period:** 2017-05-08 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142355

## Citation

> US National Institutes of Health, RePORTER application 10142355, Host Response and Immunity to Yersenia pestis Infection (5R01AI129996-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10142355. Licensed CC0.

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