# Defining the impact of Extracellular Vesicles on inflammation during pneumonic plague

> **NIH NIH F31** · UNIVERSITY OF LOUISVILLE · 2024 · $35,848

## Abstract

PROJECT SUMMARY/ABSTRACT
During infection, immune cells rely on communication to productively target and eliminate invading pathogens.
Extracellular vesicles (EVs) are one key mediator of intercellular communication between immune cells. These
membrane-bound vesicles contain proteins, lipids, and nucleic acids that represent the inflammatory state of a
given cell. Upon release, these EVs can fuse with other immune cells, establishing biochemical communication
between cells and amplifying the inflammatory response to augment pathogen clearance. Yersinia pestis is the
etiologic agent of the human disease known as plague. A hallmark of this disease is the sophisticated
suppression of the host immune system in a biphasic manner. During acute infection, Y. pestis utilizes its type 3
secretion system (T3SS) to inject effector proteins into host cells which disrupt signaling pathways essential for
bacterial clearance. Thus, acute infection is hallmarked by the maintenance of a non-inflammatory environment
in which the bacteria can proliferate without host intervention. The second stage of infection, the pro-
inflammatory phase, begins 36-48 hours post-infection, in which the host begins to successfully mount an
immune response against the pathogen. However, the bacterial load ultimately overwhelms the host delayed
responses, at which point the host may succumb to infection. Previous work has demonstrated that the
generation of this non-inflammatory environment during acute infection is essential for Y. pestis virulence. While
numerous studies have highlighted the importance of suppressing phagocytosis, exocytosis, and other
antibacterial responses, there is a gap in knowledge of how Y. pestis manipulates the EV response and how this
impacts intercellular communication. Preliminary studies suggest that Y. pestis can manipulate the proteins
packaged into EVs by neutrophils in vitro. These data support the hypothesis that Y. pestis disrupts EVs
production during infection to alter inflammation. The studies presented here will expand on our preliminary data
by delineating the in vivo EV response during pneumonic plague (Aim 1) and defining the impact of EVs on
immune modulation (Aim 2). These studies will be the first to investigate the role of EV-mediated intracellular
communication during plague. Therefore, completion of these aims will significantly improve our understanding
of how. Y. pestis exploits EV trafficking to manipulate the host immune response.

## Key facts

- **NIH application ID:** 10983732
- **Project number:** 5F31AI178999-02
- **Recipient organization:** UNIVERSITY OF LOUISVILLE
- **Principal Investigator:** Katelyn Renee Sheneman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $35,848
- **Award type:** 5
- **Project period:** 2023-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10983732

## Citation

> US National Institutes of Health, RePORTER application 10983732, Defining the impact of Extracellular Vesicles on inflammation during pneumonic plague (5F31AI178999-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10983732. Licensed CC0.

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