# Immune regulation of the transcriptional and spatial profile of Clostridioides difficile

> **NIH NIH R21** · UNIVERSITY OF PENNSYLVANIA · 2022 · $203,125

## Abstract

Project Summary
Clostridiodies difficile is an opportunistic pathogen that can colonize a patient’s gastrointestinal tract following
antibiotic perturbation of the intestinal microbiome. The quality of the host immune response to infection is an
important factor in determining disease outcome. Immunodeficiencies leave the host acutely susceptible to
infection, while unregulated host inflammation can drive disease (28). Interestingly, numerous clinical and
animal studies have found the host immune response limits C. difficile-mediated tissue damage but does not
directly drive pathogen clearance (4-12). However, the potential for host immune factors to shape C. difficile
biology beyond total pathogen burden remains largely undefined. Previous studies have demonstrated that the
biogeography and transcriptional activity of other pathogenic intestinal bacteria within the intestinal tract can be
shaped by the mucosal immune system (13-16). Whether immunologic pressures shape C. difficile spatial
and transcriptional profile has not been explored. This proposal utilizes distinct immunodeficient mice
previously reported to exhibit a spectrum from mild to severe disease upon C. difficile infection despite
indistinguishable C. difficile burden or toxin production. The aims of this proposal will first, visualize and
quantify the C. difficile vegetative and spore burden in the mucus layer compared to the central lumen of the
intestine under distinct immunologic conditions. Second, in complementary studies, the in vivo transcriptional
profile of C. difficile will be assessed in mice harboring distinct immunologic deficiencies. Transcriptional
pathways that promote sporulation, virulence factors, nutrient uptake, antimicrobial detoxification, and
metabolic activity will be examined to understand how C. difficile responds to immune pressure to promote
persistence and transmission. These aims will reveal novel immune-C. difficile interactions that determine
disease severity and provide a template for how the immune response can be modulated to support
conventional antibiotic treatment in treating C. difficile associated disease.
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## Key facts

- **NIH application ID:** 10448396
- **Project number:** 5R21AI164385-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Michael C. Abt
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $203,125
- **Award type:** 5
- **Project period:** 2021-07-09 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448396

## Citation

> US National Institutes of Health, RePORTER application 10448396, Immune regulation of the transcriptional and spatial profile of Clostridioides difficile (5R21AI164385-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10448396. Licensed CC0.

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