# Neuro-immune interactions at the intestinal surface

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2020 · $519,541

## Abstract

Project Summary
The gastrointestinal (GI) tract comprises the largest environmental interface of the body; its immune system is
posed with the unique challenge of maintaining tolerance to dietary and microbial antigens while remaining
poised to protect against pathogen invasion. Coordinated resistance and tolerance mechanisms serve to prevent
pathogenic dissemination, limit excessive GI damage, and initiate recovery responses induced by pathogenic
burden or injury. The GI tract hosts as many neurons (enteric-associated neurons, EANs) as the spinal cord and
more immune cells than all other compartments together. EANs include sensory neurons, interneurons, and
motor neurons with cell bodies within (intrinsic) or outside the intestine (extrinsic), which control a variety of
functions within the GI tract. EANs are often targeted by enteric pathogens, resulting in functional gastrointestinal
disorders post pathogen clearance. The clinical presentations of post-infectious enteric neuronal damage include
unresolved low-grade intestinal inflammation, gastrointestinal motility impairment, and nerve damage.
Nevertheless, the underlying mechanisms involved in infection–induced neuronal damage are incompletely
understood. Our recent data indicates that murine enteric infection results in a rapid and persistent loss of iEANs,
which is associated with prolonged gastrointestinal changes including intestinal dysmotility. However, infection
history and microbiota composition can prevent iEAN loss or accelerate iEAN recovery, respectively; findings
that may lead to a better understanding of human post-infectious IBS and additional disorders associated with
EAN damage during inflammation. Imaging analyses suggested a subtype–specific neuronal loss upon
Salmonella infection, and transcriptomics and genetic approaches indicated an iEAN cell death mechanism that
is dependent on components of the inflammasome pathway. Depletion of intestinal muscularis macrophages
(MMs), located in close proximity to enteric neurons, as well as targeting of β2-AR on myeloid cells, resulted in
enhanced infection-induced neuronal loss, suggesting a functional role for a MM tissue protective program
induced upon infection. Our observations suggest a functional role for neuron–macrophage interactions in
limiting infection-induced neuronal damage or accelerating neuronal recovery, supporting the significance and
impact of this proposal. We will characterize mechanisms underlying neuronal cell death post enteric infection
with different pathogens (Aim 1). We will also to define how microbiota manipulations can rescue neuronal death
post infection, possibly defining a role for specific bacterial species in this process (Aim 2). Finally, we will
investigate the cellular and molecular immune mechanisms regulating neuronal loss during heterologous
secondary infections (Aim3). By utilizing imaging, cell sorting–independent transcriptomics, single-cell
approaches and genetic gain– and loss–of-func...

## Key facts

- **NIH application ID:** 10071717
- **Project number:** 1R01DK126407-01
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Daniel S Mucida
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $519,541
- **Award type:** 1
- **Project period:** 2020-07-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071717

## Citation

> US National Institutes of Health, RePORTER application 10071717, Neuro-immune interactions at the intestinal surface (1R01DK126407-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10071717. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*