# Mucosal Immune Defense Mechanisms of the Urinary Bladder

> **NIH NIH U01** · WASHINGTON UNIVERSITY · 2020 · $1,460,729

## Abstract

PROJECT SUMMARY
Mucosal surfaces must allow the exchange of metabolites required for life into the host and
excretion/exclusion of wastes and toxins out of the host, while also maintaining a first line of
defense against invasive microbes. However, mucosal inflammation, elicited to combat
microbial infection, can also damage the integrity of the mucosal barrier, if not controlled. Many
mucosal surfaces are in constant or transient contact with microbes, yet the molecular
mechanisms governing the extent of the inflammatory response at the mucosal surface, the
healing of the surface after insults and the molecular basis of remodeling changes that affect
subsequent mucosal function and inflammatory responses are poorly understood. This proposal
will investigate these mechanisms by assembling an experienced team of investigators with
diverse and complimentary expertise to further our understanding of the mucosal immune
defense mechanisms of the urinary bladder against bacterial infection. Analysis of the bladder
mucosal responses to the most common cause of urinary tract infection (UTI), E. coli, in
distantly related inbred mouse strains has identified patterns of response that correlate with
resistance or susceptibility to both initial and secondary infections. The proposed research will
probe differences in the immune defense pathways of the bladder mucosa during acute and
recurrent infection, providing critical insights in the field of mucosal immunology and the role of
epithelial cells in mucosal response. These studies will specifically investigate the role of
bladder mucosal remodeling in modulating innate signaling pathways in previously infected mice
(Aim 1) and investigate the protective (Aim 2) and damaging (Aim 3) mechanisms of the acute
bladder inflammatory response in naïve mice. These responses correlate with outcomes of
disease and subsequent remodeling of the bladder tissue, which in turn affects subsequent
infections. Understanding immune responses of previously infected vs. naïve mucosal tissues
will likely give important insights into clinical disease, in which patients over their life-time have
undoubtably suffered from multiple sequential infections. These investigations will reveal new
details of the mechanisms of mucosal defense against bacteria, broadening the understanding
of the regulation of mucosal inflammation and the signaling between mucosal epithelia and
immune cells, and thus advance our understanding of acute and recurrent infection
susceptibility and protection, in this age of increasing microbial antibiotic resistance. These
insights will contribute to the development of novel vaccines and immunomodulatory
therapeutics targeting the mucosa.

## Key facts

- **NIH application ID:** 9941018
- **Project number:** 5U01AI095542-10
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** MARCO COLONNA
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,460,729
- **Award type:** 5
- **Project period:** 2011-07-05 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9941018

## Citation

> US National Institutes of Health, RePORTER application 9941018, Mucosal Immune Defense Mechanisms of the Urinary Bladder (5U01AI095542-10). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9941018. Licensed CC0.

---

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