# Targeting Siglec-9/E for therapy of sepsis

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2021 · $380,000

## Abstract

Sepsis is generally defined as a systemic inflammatory response syndrome triggered by microbial infection.
Severe sepsis (septic shock) can be a life-threatening condition, and approximately 200,000 deaths annually are
attributed to sepsis in the US alone. Despite the availability of the treatment for sepsis with antibiotic therapy,
inotropes, fluid resuscitation and end-organ support, there is a critical need for targeted and effective sepsis
therapy to reduce mortality from this disease. The Toll-like receptor (TLR) family is responsible for detecting
pathogens and inducing innate and adaptive immunity, while sialic acid-binding immunoglobulin superfamily lectin
receptors (Siglecs) provide negative regulation for the immune response. Recently, we reported extensive and
direct interactions between these pattern recognition receptors (PRRs). The most promiscuous TLR binders were
human Siglecs 5 and 9. We have observed that the dendritic cells (DCs) from Siglece (mouse homologue of the
human Siglec-9) deficient mice demonstrated increased responses to all TLR ligands tested and that Siglec-E
negatively regulates the activation of TLR4 by controlling its endocytosis, suggesting that Siglec-E may play an
important role in TLR-related sepsis development. To elucidate the function of this novel pathway in sepsis
development, our research focuses on the molecular mechanism of the Siglec-E-TLR interaction in controlling
bacterial infection-induced sepsis. Thus, in this project, we plan to: 1) examine the underlying molecular
mechanism by which Siglec-E regulates infection-induced TLRs endocytosis; 2) Functional analysis of Siglec-E-
mediated TLRs endocytosis and degradation during infection; 3) explore novel therapeutic strategies for the
treatment of sepsis. These studies will not only reveal the molecular mechanism of the Siglec-E-TLRs pathway in
infection-induced TLRs endocytosis, but will also translate our knowledge from basic science research into the
clinical treatment of sepsis.

## Key facts

- **NIH application ID:** 10158272
- **Project number:** 5R01AI137255-04
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** Guoyun Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $380,000
- **Award type:** 5
- **Project period:** 2018-06-08 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158272

## Citation

> US National Institutes of Health, RePORTER application 10158272, Targeting Siglec-9/E for therapy of sepsis (5R01AI137255-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10158272. Licensed CC0.

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