Investigating the role of interferon lambda in protection against severe clostridioides difficile infection
Ended Project Grant Awarded Last action
- Award ID
- F31DK138546
- Recipient
-
The Trustees Of The University Of Pennsylvania UEI GM1XX56LEP58
- Awarding agency
-
National Institute of Diabetes and Digestive and Kidney Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $174,015
Award facts
- Assistance listing
- 93.847 Diabetes, Digestive, and Kidney Diseases Extramural Research
- Completion date
- Place of performance
- Philadelphia, PA 19104, USA
Award details come from USAspending.gov.
Description
- Abstract
- Clostridioides difficile is the leading cause of hospital-acquired gastrointestinal infections in the united states. Pathogenesis is mediated by secreted toxins that cause the death of intestinal epithelial cells (iecs) and breakdown of the intestinal barrier. C. Difficile infection is primarily treated with antibiotics; however, the high rate of recurrent infections necessitates alternative treatment options. Our lab has found that orally administering a toll-like receptor 7 (TLR7) agonist, R848, protects mice against severe disease following lethal c. Difficile challenge. R848 treatment induces the expression of inflammatory cytokines including interferons. Interestingly, while protection was not dependent on type i or type II interferon signaling, we found that mice deficient for type III interferon (IFN-) signaling are not protected following R848 treatment. While IFN- is best known for its role in antiviral immunity, recent works by others has shown that IFN- stimulates intestinal stem cell proliferation to reduce the severity of experimental colitis. This proposal seeks to determine the mechanism by which IFN- contributes to R848-mediated protection against c. Difficile infection. The overarching hypothesis for this project is that IFN- directly acts on iecs to stimulate stem cell proliferation and thereby repairing the damage to the intestinal barrier from c. Difficile toxin. Aim 1 will identify the critical cell type that responds to IFN- for R848-mediated protection against c. Difficile infection using bone marrow chimeric mice and cell- lineage specific knockout mice. Aim 2 will test the hypothesis that IFN- promotes intestinal stem cell function and stimulates proliferation by utilizing LGR5EGFP reporter mice and intestinal organoid culture models. This project will elucidate the mechanism behind a novel role for IFN- in the immune response against c. Difficile and may inform future development of therapeutics against this major public health threat.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | -$17,729 | |
| Amendment | -$25,565 | |
| Amendment | -$25,565 | |
| Amendment | $49,538 | |
| Amendment | $1,280 | |
| Amendment | $1,280 | |
| Amendment | $47,694 | |
| Amendment | $0 | |
| Amendment | $47,694 | |
| Amendment | $47,694 | |
| Amendment | $0 | |
| Amendment | $47,694 | |
| Original award | $0 |
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Quick answers
Who received award F31DK138546?
F31DK138546 was awarded to The Trustees Of The University Of Pennsylvania by National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health) on May 15, 2024.
How much is award F31DK138546 worth?
$174,015 has been obligated on F31DK138546.
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