# The Role of Route of Entry by Bacterial Antigens on Colonic T Cell Responses

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2022 · $552,708

## Abstract

Project Summary
Effector T cell responses to pathogenic bacteria are crucial for protection from pathogens, but when directed
toward non-pathogens, may underlie inappropriate responses driving disorders such as inflammatory bowel
disease (IBD). Conversely, Foxp3+ regulatory T cell (Treg) responses to commensals enforce tolerance to
prevent immune-mediated pathology such as IBD. The relative priority and context of gut bacterial interaction
with the immune system remain significant gaps in our understanding. We observed that dysbiosis induces the
formation of colonic goblet cell associated antigen passages (GAPs), providing an alternative route by which
the immune system encounters gut resident bacteria. Further, we observed that gut resident bacteria taxa
generally considered as tolerance-promoting can induce effector responses when encountered via colonic
GAPs. Alternatively, we have found that antigen-specific peripheral (pTregs) largely recognize mucosal
associated (MA) murine Helicobacter spp in vitro and in vivo, and that encounter of Helicobacter spp occurs
continuously and is independent of GAPs. These data indicate that bacteria believed to be pathobionts can be
potent inducers of pTregs during homeostasis, and in contrast, taxa believed to be tolerance inducing,
Clostridia, are largely not encountered by the immune system in the steady state, but are encountered via
colonic GAPs resulting in effector T cell responses. We hypothesize that the location and route of encounter of
gut bacteria are important determinants of the outcome of immune responses and that the MA bacteria can
play an important role in controlling the interactions and responses to gut resident bacteria encountered via
colonic GAPs. In this proposal we will evaluate this hypothesis by: 1) defining the commensal antigens
delivered via mucosal association (MA) and GAPs 2) defining the dendritic cell (DC) subsets involved in
acquisition and presentation of mucosal associated and GAP delivered commensal antigens and 3) defining
the effects of Helicobacter on the mucosal immune system and responses to GAP delivered antigens. Studies
outlined in this proposal will fill the gaps in our understanding by identifying how specific bacterial taxa are
encountered by the immune system and the subsequent immune responses. This knowledge can be leveraged
to guide manipulations of the gut microbiota and the immune system to ‘reset’ chronic inflammatory responses
and return to homeostasis.

## Key facts

- **NIH application ID:** 10396536
- **Project number:** 5R01AI136515-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** CHYI S HSIEH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $552,708
- **Award type:** 5
- **Project period:** 2018-05-23 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10396536

## Citation

> US National Institutes of Health, RePORTER application 10396536, The Role of Route of Entry by Bacterial Antigens on Colonic T Cell Responses (5R01AI136515-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10396536. Licensed CC0.

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