# Malaria and allergic inflammatory changes to the gut barrier

> **NIH NIH R01** · UNIVERSITY OF IDAHO · 2020 · $472,901

## Abstract

PROJECT SUMMARY/ABSTRACT
Bacteremia associated with malaria is a significant cause of mortality among children in sub-Saharan Africa
and is also prevalent in adults in some malarious regions. Bacteremic children and adults are difficult to identify
and many have blood infections with isolates that are multi-antibiotic-resistant. The high occurrence of
bacteremia suggests that malaria induces a “leaky gut,” an intestinal barrier dysfunction that facilitates escape
of bacteria from the gut lumen into the blood with resulting serious sequelae. Recent studies have
documented allergic inflammation in malaria, but no studies to date have linked this phenomenon to increased
intestinal permeability observed in both acute and resolving clinical malaria. Our published and preliminary
studies suggest that malaria-induced innate signals, including early cytokine synthesis and basophil activation,
lead to mast cell influx into the intestine. Here, activated mast cells damage the physical barrier and suppress
host immune responses that limit spread of enteric bacteria that cross the damaged physical barrier. In these
studies, we will use our established models to examine the contributions of early innate signals and basophils
– cells for which no function in malaria has been described – in promoting mastocytosis and the leaky gut
phenotype we have observed. We will also determine to what extent malaria-induced mast cell degradation of
the physical and immunological barriers of the intestine is dependent on mast cell proteases and mast cell-
derived cytokines that are relevant to our observations. It is our expectation that our work will elucidate new
mechanisms underlying the importance of allergic inflammation to mucosal barrier degradation in malaria. The
outcome of the proposed research is likely to provide novel paradigms for future interventions to reduce the
incidence of malaria-associated bacteremia. This work is significant because it directly addresses an important
co-morbidity of malaria and will provide novel mechanistic insights into well-documented – and heretofore
unlinked – clinical observations.

## Key facts

- **NIH application ID:** 9933795
- **Project number:** 5R01AI131609-03
- **Recipient organization:** UNIVERSITY OF IDAHO
- **Principal Investigator:** Shirley Luckhart
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $472,901
- **Award type:** 5
- **Project period:** 2018-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933795

## Citation

> US National Institutes of Health, RePORTER application 9933795, Malaria and allergic inflammatory changes to the gut barrier (5R01AI131609-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9933795. Licensed CC0.

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