# Innate immune defense against clostridium Difficile Infection

> **NIH NIH R01** · UNIVERSITY OF CHICAGO · 2020 · $408,564

## Abstract

Project Summary/Abstract
Clostridium difficile is a leading cause of diarrhea in hospitalized patients and infection is acquired by
ingestion of spores that germinate into toxin-producing vegetative forms that destroy colonic
epithelial integrity. Intestinal inflammation induced by C. difficile requires spore germination within
the GI tract, bacterial proliferation and toxin production leading to intestinal epithelial damage. C.
difficile growth in the colon occurs when the composition of the commensal bacterial flora is
damaged by antibiotic treatment. Specific members of the commensal flora inhibit C. difficile growth,
in part by converting primary to secondary bile salts. Once C. difficile infection has damaged the
colonic epithelial layer, the host’s immune system is activated and, while essential for host survival,
also contributes to intestinal pathology. Inflammatory monocytes, neutrophils, innate lymphocytes
(ILCs) and a range of inflammatory cytokines have been implicated in defense against C. difficile
infection (CDI) and in inflammatory pathology. The goal of our studies is to identify and characterize
microbiota and immune-mediated protective mechanisms and to test our discoveries on
microbiologically and clinically diverse C. difficile strains. Our specific aims are: 1.) To assemble
minimal-complexity commensal bacterial consortia derived from human fecal samples that provide
high-level resistance against CDI. 2.) To characterize microbiota-mediated mechanisms that
promote ILC1-mediated resistance against C. difficile and to test the hypothesis that the residual
microbiota determines the balance of ILC1 versus ILC3 differentiation. 3.) To determine whether
microbiota or ILC1 mediated defenses against CDI differ for distinct C. difficile strains. The proposed
studies will provide novel insights into microbiota-mediated defenses against CDI and will also
identify immune mechanisms that ameliorate adverse inflammatory responses during early CDI.
These insights will facilitate the development of therapies to prevent and treat C. difficile infections.

## Key facts

- **NIH application ID:** 9971430
- **Project number:** 5R01AI095706-10
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Eric G. Pamer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $408,564
- **Award type:** 5
- **Project period:** 2012-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971430

## Citation

> US National Institutes of Health, RePORTER application 9971430, Innate immune defense against clostridium Difficile Infection (5R01AI095706-10). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9971430. Licensed CC0.

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