# Yersina perstis interactions with macrophages

> **NIH NIH P20** · UNIVERSITY OF NORTH DAKOTA · 2024 · $181,667

## Abstract

Plague, an emerging infectious disease endemic to multiple continents, including North 
and South America, is a top priority in national biodefense. Studying pathogenic yersiniae, the 
bacteria responsible for plague, provides valuable insights into pathogenesis and evolution. 
Genomic sequencing of the Yersinia genus and extensive Yersinia pestis genomes spanning 
from the Bronze Age to the present offer a rich resource for this research. 
A distinct feature of plague infections is the lack of inflammation at bacterial replication 
sites. Recent studies on pneumonic plague reveal a two-phase course: a delayed inflammatory 
response followed by a highly inflammatory phase as the disease progresses. In the initial 
phase, non-human primate and mouse models show no cellular infiltration. Extracellular 
presence of Y. pestis in primate lungs does not trigger inflammation. In a rat model of bubonic 
plague, neutrophil infiltration into draining lymph nodes is delayed, and infected sites undergo 
necrosis instead of inflammation. Comparisons between Y. pseudotuberculosis and Y. pestis 
infections demonstrate neutrophil recruitment but inadequate containment of the infection. 
Research on the type III secretion system and other virulence factors has explored their role in 
neutralizing early inflammatory responses. However, understanding macrophage polarization 
during early plague stages remains incomplete. A central hypothesis suggests that Y. pestis 
prevents inflammation by inhibiting M1 polarization or inducing M2 macrophages Investigating 
these mechanisms will enhance knowledge of how macrophage polarization contributes to early 
immune suppression in plague, preventing the infiltration of polymorphonuclear leukocytes 
(PMNs) and promoting the initial anti-inflammatory stage of plague. 
Aim 1. Investigate macrophage polarization after Yersinia pestis exposure to block 
inflammation by either inhibiting M1 polarization or inducing M2 macrophages. 
Aim 2. Determine signaling pathways induced and mechanisms used by Y. pestis to 
influence macrophage polarization. 
Aim 3. Examine the virulence factors utilized by Y. pestis to polarize macrophages.

## Key facts

- **NIH application ID:** 11009894
- **Project number:** 5P20GM113123-09
- **Recipient organization:** UNIVERSITY OF NORTH DAKOTA
- **Principal Investigator:** Catherine Ayn Brissette
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $181,667
- **Award type:** 5
- **Project period:** 2016-05-13 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11009894

## Citation

> US National Institutes of Health, RePORTER application 11009894, Yersina perstis interactions with macrophages (5P20GM113123-09). Retrieved via MORVS 2026-10-26 from https://api.morvs.ai/grant/nih/11009894. Licensed CC0.

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