# Molecular mechanisms of Salmonella mediated autoimmunity

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $384,550

## Abstract

Summary
 Chronic autoimmune diseases occur when the immune system recognizes self-
antigens as foreign, leading to inflammation and destruction of specific tissues and
organs. Although the etiology of many chronic autoimmune diseases is generally
unknown, there are many examples of diseases in which bacterial infections initiate
or exacerbate autoimmune responses. One of the well-described autoimmune
conditions that develop in response to an infection is reactive arthritis (ReA), also
known as post-infectious arthritis or ankylosing spondylitis. Following
gastrointestinal infections with enteric pathogens such as Salmonella, Shigella, or
Yersinia, 5-10% of patients develop ReA, a painful form of inflammatory arthritis. By
using Salmonella enterica serovar Typhimurium (STm) as a model organism, we
discovered that a STm amyloid surface structure involved in biofilm formation, curli
fibrils, form stable complexes with DNA, and that the curli/DNA complexes are
potent stimulators of autoimmunity. Systemic exposure to these complexes triggers
an autoimmune response characterized by the production of type I interferons
(IFNs) and anti-double stranded DNA (anti-dsDNA) autoantibodies.
 The primary objective of this application is to investigate the mechanisms by
which curli/DNA complexes are recognized by the immune system and trigger
autoimmunity following gastrointestinal infection. Here, we hypothesize that that
the production of curli in the gut by the invasive STm leads to autoimmune sequelae
by triggering epithelial damage and activating TLR2 and TLR9, which in turn results
in the upregulation of type-I IFN and of type-17 immunity. In aim 1, we will
determine the role of curli-expressing bacteria and of curli/DNA complexes in the
development of autoimmunity. In aim 2, we will identify the immune pathways that
contribute to the autoimmunity induced by STm infection. In aim 3, we will
determine whether genetic susceptibility to autoimmunity enhances the immune
activation by curli/DNA complexes.

## Key facts

- **NIH application ID:** 10031214
- **Project number:** 1R01AI153325-01
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Cagla Tukel
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $384,550
- **Award type:** 1
- **Project period:** 2020-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10031214

## Citation

> US National Institutes of Health, RePORTER application 10031214, Molecular mechanisms of Salmonella mediated autoimmunity (1R01AI153325-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10031214. Licensed CC0.

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