# Mechanisms underlying poor skin host defense in diabetic conditions

> **NIH NIH R21** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $254,580

## Abstract

Summary
Infections caused by both methicillin resistant (MRSA) and susceptible (MSSA) forms of Staphylococcus aureus
are more frequent and severe in people with diabetes than in healthy individuals and represent a leading cause
of hospitalization. A hallmark of S. aureus skin infection is the formation of an abscess that is formed by live and
necrotic neutrophils, bacteria, cell debris and a capsule of fibrin/collagen. Abscess formation must be tightly
regulated to prevent microbial dissemination. Since the early 1900’s, it has been shown that phagocytes from
people with diabetes are unable to ingest and kill bacteria, which created the paradigm that diabetes leads to
immunosuppression. Here, we will take our current knowledge in host defense and diabetes in a different
direction. We speculated that increased susceptibility to infection is due to an uncontrolled inflammatory
response that cause skin damage and prevents bacterial elimination. Our surprisingly published and preliminary
data suggest that enhanced lesion size and bacterial load in the skin of MRSA-infected diabetic mice correlated
with exaggerated nonproductive neutrophil migration to the site of infection and a lack of well-defined abscesses.
Our central hypothesis is that hyperglycemia induces an enhanced and persistent inflammatory response to S.
aureus skin infection due to inefficient efferocytosis. We propose the following specific aims: 1) Determine the
role of high glucose in poor abscess formation and inadequate host defense during S. aureus skin infection in
diabetic mice. 2) Assess the mechanisms involved in cell death elimination and exaggerated inflammatory
response during S. aureus skin infection in diabetic mice. We will employ a series of pharmacologic and genetic
approaches, associated with imaging mass spectrometry (IMS), immunohistochemistry and flow cytometry to
unveil novel interactions among macrophages and the production of inflammatory molecules that might dictate
phagocyte recruitment and abscess formation in both diabetic and nondiabetic mice. After this project, we expect
to have delineated a framework for further dissecting the dynamics of poor skin host defense that may improve
our understanding of innate immune responses and their potential for therapeutic manipulation in diabetes. We
should then be positioned to take this work further in both basic and translational directions.

## Key facts

- **NIH application ID:** 9875959
- **Project number:** 1R21AI149207-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** C. Henrique Serezani
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $254,580
- **Award type:** 1
- **Project period:** 2020-01-16 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9875959

## Citation

> US National Institutes of Health, RePORTER application 9875959, Mechanisms underlying poor skin host defense in diabetic conditions (1R21AI149207-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9875959. Licensed CC0.

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