# Immune responses to commensal bacterial spores in the intestinal mucosa

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $248,773

## Abstract

PROJECT SUMMARY/ABSTRACT
Many bacterial species in the phylum Firmicutes produce spores. The spores of commensal and pathogenic
bacteria play a crucial role in host entry and the initial encounter with the immune system. How bacterial
spores interact with host immunity, however, remains poorly understood. In the proposed research project, we
investigate spore-immune interactions and their impact on inflammation and tissue homeostasis in the
intestinal mucosa. We discovered that RNA-sensing toll-like receptors (TLRs)—TLR7 and TLR13 in mice and
their human counterparts—played a crucial role in detecting and triggering immune responses to the spores of
Bacillus anthracis (BA), the etiologic agent of anthrax. BA spores harbored high amounts of RNA whose TLR-
stimulating activity was retained after extraction and purification. This RNA was mainly located in the outermost
layer of the spore, or the exosporium. TLR7/13 sensing of BA spores led to type I interferon (IFN-I) production
from host cells. These findings prompted us to search commensal bacterial spores for similar structural
features and functional properties. For this investigation, we devised a novel protocol that enabled spore
isolation from fecal samples or intestinal luminal contents without ex vivo culture. This protocol allowed us to
detect gut microbiota-derived spores with high RNA content and IFN-I-inducing capacity. These findings, in
conjunction with the emerging evidence that "tonic" IFN-I signaling protects against colitis, colon cancer, and
enteric viral infection, led us to formulate the central hypothesis that TLR sensing of spore-associated RNA is a
pivotal mechanism by which commensal bacterial spores induce IFN-I-dependent tissue-protective responses
in the intestinal mucosa. In the proposed research, we will verify the central hypothesis by pursuing the
following specific aims: to identify the commensal bacterial species in the mouse and human gut whose spores
possess an RNA-laden exosporium and IFN-I-inducing activity (Aim #1); and to establish the role of
commensal bacterial spores and spore-sensing TLRs in inducing IFN-I production and suppressing
inflammatory damage in the intestinal mucosa (Aim #2). Our study will advance our understanding of mucosal
physiology and pathology by identifying commensal bacterial spores as major inducers of intestinal IFN-I
production and demonstrating their role in immune regulation and tissue protection.

## Key facts

- **NIH application ID:** 10041895
- **Project number:** 1R21AI153985-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jin Mo Park
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $248,773
- **Award type:** 1
- **Project period:** 2020-05-22 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10041895

## Citation

> US National Institutes of Health, RePORTER application 10041895, Immune responses to commensal bacterial spores in the intestinal mucosa (1R21AI153985-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10041895. Licensed CC0.

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