# Dissemination of intracellular and extracellular Listeria from the gut

> **NIH NIH R21** · UNIVERSITY OF KENTUCKY · 2022 · $229,500

## Abstract

Foodborne transmission of the facultative intracellular bacterial pathogen Listeria monocytogenes (Lm)
results in human disease that ranges in severity from mild gastroenteritis to life-threatening septicemia or
meningoencephalitis. The host and bacterial factors that determine disease severity are not well defined,
and our understanding of the intestinal phase of listeriosis, in particular, is severely limited. To address this
knowledge gap, we developed a mouse model of foodborne Lm infection that closely mimics all phases of
the human disease. In preliminary studies, we found that the majority of Lm in the gut were extracellular,
and that Lm was not able to replicate in many of the mononuclear phagocyte subsets present in the intestinal
lamina propria. This was an unexpected result, because intracellular growth and spread from cell-to-cell
without encountering the extracellular milieu are generally regarded as the primary virulence strategies for
Lm. The overall hypothesis of this proposal is that foodborne Lm can use one of three distinct pathways to
disseminate from the intestinal lamina propria to the mesenteric lymph nodes (MLN): 1) Lm “hitch a ride”
attached to migratory inflammatory Ly6Chi monocytes which they cannot efficiently invade; 2) Lm invade
conventional dendritic cells (cDC) which serve as a “Trojan horse” to deliver non-replicating, but intracellular
bacteria to the MLN; and 3) extracellular Lm traffic free-flowing through lymphatic vessels to the subcapsular
sinus of the MLN. We propose that these three pathways are likely to be redundant during in vivo infection,
but may be influenced by the route used by Lm to invade the intestinal epithelium. In Aim 1, the role of cell-
associated vs. free-flowing extracellular bacteria in promoting dissemination to the MLN that drain either the
ileum or the colon will be determined. In Aim 2, we will determine how the dissemination pathway used by
Lm affects the ability of the bacteria to survive and replicate in the MLN and to promote further systemic
spread. These exploratory studies will advance the field by defining the mechanisms used by Lm to avoid
clearance in the MLN a critical bottleneck to avoid systemic spread of orally acquired pathogens.

## Key facts

- **NIH application ID:** 10417246
- **Project number:** 5R21AI155824-02
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** SARAH E. F. D'ORAZIO
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $229,500
- **Award type:** 5
- **Project period:** 2021-06-04 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10417246

## Citation

> US National Institutes of Health, RePORTER application 10417246, Dissemination of intracellular and extracellular Listeria from the gut (5R21AI155824-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10417246. Licensed CC0.

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