# Immune Interactions with the Mucus-Associated Microbiota

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $448,117

## Abstract

PROJECT SUMMARY/ABSTRACT
The disorders collectively referred to as inflammatory bowel disease (IBD) are characterized by aberrant
immune responses to the commensal microbiota. The establishment and maintenance of tolerance to the
microbiota is accomplished via a complex and dynamic network of cells and molecules that collectively stave
off immune reactivity. Elucidation of the mechanisms whereby these natural pathways limit immunity to
normally benign commensals, especially those that occupy niches at the epithelial border, will ultimately
enhance our ability to target these interactions for the prevention and/or treatment of intestinal inflammation.
We hypothesize that high-affinity, thymus-dependent (T-dependent) antibody responses are essential for the
regulation of mucus-associated bacterial communities. T-dependent antibody responses are especially
important in the host response to pathogenic invasion of the gut. Since some helpful commensal species
utilize similar mechanisms as pathogens to establish a niche in the mucus layer lining the intestinal epithelium,
it stands to reason that similar immune mechanisms are deployed to control these organisms. We have found
that mice colonized with a minimal mucus-associated consortium display a predominantly T-dependent IgG
response. Moreover, mice with impaired production of T-dependent antibodies have significantly diminished
total antibody responses to antigens derived from mucus-associated bacteria including specific flagellins
derived from members of the family Lachnospiraceae. Colonization with mucus-associated bacteria, or the
deficiency of T-dependent antibodies in the presence of such organisms, coincides with increased production
of the immunoregulatory cytokine interleukin-10 (IL-10) by CD4 T cells in the large intestine. Accordingly,
simultaneous disruption of these 2 pathways results in spontaneous colonic inflammation. In this proposal, we
will utilize defined microbes and the antigens they generate to elucidate the mechanisms whereby interactions
between flagellated mucus-associated bacteria and the gut immune system promote tolerance of these
communities. In addition, we will explore novel roles for T-dependent anti-commensal IgG1 in the
establishment and maintenance of immune homeostasis. If successful, our studies will define the mechanisms
whereby TD anti-commensal antibodies promote immune normalcy at the colonic epithelial border and
constantly mitigate the risk of deleterious reactivity to the diverse community of mucus-associated bacteria.

## Key facts

- **NIH application ID:** 10879110
- **Project number:** 5R01AI162736-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Craig L Maynard
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $448,117
- **Award type:** 5
- **Project period:** 2021-07-12 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10879110

## Citation

> US National Institutes of Health, RePORTER application 10879110, Immune Interactions with the Mucus-Associated Microbiota (5R01AI162736-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10879110. Licensed CC0.

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