# The molecular mechanism of Siglec-E in bacterial clearance

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2024 · $462,000

## Abstract

Sepsis is a systemic inflammatory response syndrome initiated by infection. Most cases of septic shock are
caused by Gram-negative bacteria, including Escherichia coli (E. coli), which remains one of the most common
pathogens leading to sepsis. Understanding the mechanisms by which the mammalian immune system
differentially responds to infection by Gram-negative and Gram-positive bacteria will place us in a better
position to treat or prevent sepsis. Members of the sialic acid-binding immunoglobulin-like lectin family
(Siglecs) are cell surface receptors that negatively regulate the response to infection by binding or taking up
sialylated pathogens; however, most pathogens are not sialylated. We previously published a study in which
we used nonsialylated bacteria to show that Siglec-E knockout (SiglecE-/-) mice exhibited higher mortality than
wild-type (WT) mice following infection by Gram-negative but not Gram-positive bacteria. Better survival in WT
mice depended on more efficient clearance of Gram-negative than Gram-positive bacteria. Moreover, infection
with Gram-negative E. coli strains 25922 and DH5α induced the expression of Siglec-E, which promoted
production of reactive oxygen species (ROS). In contrast, infection with Gram-positive bacteria Staphylococcus
aureus or Listeria monocytogenes reduced expression of Siglec-E, which inhibited production of ROS. Based
on these findings, we designed this project to: 1) Elucidate the molecular mechanisms of Siglec-E in bacterial
clearance; 2) Dissect the molecular mechanisms underlying differential regulation of innate immune response
during infection with Gram-positive and Gram-negative bacteria by controlling Siglec-E; 3) Evaluate Siglec-E
as a therapeutic target for the treatment of bacterial sepsis by using CLP. These studies will not only reveal the
molecular mechanisms of the novel role of Siglec-E in bacterial clearance but also provide novel approaches
toward treatment of bacterial induced-sepsis.

## Key facts

- **NIH application ID:** 10974823
- **Project number:** 1R01AI179632-01A1
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Guoyun Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $462,000
- **Award type:** 1
- **Project period:** 2024-06-13 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10974823

## Citation

> US National Institutes of Health, RePORTER application 10974823, The molecular mechanism of Siglec-E in bacterial clearance (1R01AI179632-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10974823. Licensed CC0.

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