# Role of the Pro-inflammatory MIF Homolog of Entamoeba histolytica in Colitis

> **NIH NIH K08** · UNIVERSITY OF VIRGINIA · 2020 · $192,024

## Abstract

Project Summary
Approach: We propose to test the hypothesis that the Entamoeba histolytica homolog of the upstream
proinflammatory cytokine macrophage migration inhibitory factor (EhMIF) mediates a destructive inflammatory
response in amebic colitis. We further hypothesize that EhMIF induces IL-8 production from intestinal
epithelial cells resulting in recruitment of inflammatory cells to the intestinal mucosa. Additionally, we predict
that EhMIF stimulates inflammatory cells in the intestinal mucosa resulting in excess TNF-α, IL-6 and IL-23
that disrupt the mucosal barrier.
Innovative aspects of the proposal include that it explores a potentially novel mediator of parasite-induced
injury at an understudied tissue site: the effect of parasite MIF homologs on intestinal mucosal inflammation
and injury during infection is not known, and challenges the dominant paradigm that intestinal mucosal injury is
a result of direct killing of host cells by E. histolytica.
Successful completion of these studies will advance our understanding of the host-E. histolytica interactions
and may translate into new approaches to immune-modulating therapies and vaccination.
Significance: The work is significant because diarrheal disease is the second leading cause of death in
children under five globally, and intestinal amebiasis is one of the main causes of severe diarrhea in the
developing world. There currently exists no vaccine and only a single class of drugs, the nitroimidazoles, to
treat this devastating disease.
The environment for the work includes the superb academic infectious diseases program of the University of
Virginia, a program of active investigation of E. histolytica in humans, murine models, and at the cellular
level, and my mentor (Dr. Petri) who like myself is an infectious diseases clinician, and who has contributed
to amebic colitis research for over 25 years.
K08: My career development plan in this proposal will augment the success of this project through the
combination of strong guidance and support from my internal and external advisory teams, courses, technical
training, seminars and conferences focusing on immunology and host-pathogen interactions, all of which will
help establish me as an independent clinician-scientist.

## Key facts

- **NIH application ID:** 9933782
- **Project number:** 5K08AI119181-05
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Shannon Moonah
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $192,024
- **Award type:** 5
- **Project period:** 2016-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933782

## Citation

> US National Institutes of Health, RePORTER application 9933782, Role of the Pro-inflammatory MIF Homolog of Entamoeba histolytica in Colitis (5K08AI119181-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9933782. Licensed CC0.

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