# Innate Recognition of Bacterial Sugars

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2020 · $350,000

## Abstract

SUMMARY/ABSTRACT
IL-1β production is essential for effective host defense against many pathogens, but can also be a source
of significant pathological inflammation. As such, the mechanisms by which IL-1β is produced are an intense
area of research interest. Secretion of IL-1β (and related cytokines such as IL-18) by phagocytes including
macrophages and dendritic cells is regulated by the formation of “inflammasome” complexes that activate
cytosolic caspase-1 to process pro-cytokine into the mature form and allow its release from the cell. This
project has been investigating the innate immune mechanisms by which peptidoglycan from gram-positive
bacterial cell walls activates the NLRP3 inflammasome. We have recently discovered that when
peptidoglycan is eaten by phagocytes, degradation and release of monomeric n-acetylglucosamine is
necessary to stimulate IL-1β release. Further, we have developed evidence that this sugar is detected in
the cytosol by hexokinase II, an enzyme involved in the first step of glycolysis. This finding suggests a new
link between mechanisms of cellular metabolism and innate sensing of microbial pathogens. In this project,
we will investigate the role of hexokinase in macrophage responses to infection with Staphylococcus aureus
in vitro and in vivo, the mechanisms by which hexokinase regulation activates the NLRP3 inflammasome,
and the role of mitochondrial permeability in the process.

## Key facts

- **NIH application ID:** 9900013
- **Project number:** 5R01GM085796-12
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** David M. Underhill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $350,000
- **Award type:** 5
- **Project period:** 2008-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900013

## Citation

> US National Institutes of Health, RePORTER application 9900013, Innate Recognition of Bacterial Sugars (5R01GM085796-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9900013. Licensed CC0.

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