# Mechanisms of Oral Streptococcus Macrophage Activation

> **NIH NIH F31** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $31,185

## Abstract

Project Summary/Abstract
Periodontal disease is a complex inflammatory disease resulting not from a single organism, but rather a
dysbiotic community of oral microbes working together to promote disease. Inflammation associated with disease
is initiated by members of the oral biofilm, but the host response to the microorganisms, including inflammatory
reactions by macrophages, is primarily responsible for disease progression. Streptococcus gordonii is a normally
innocuous inhabitant of the oral cavity but is also involved in the progression of periodontal disease, partially by
promoting colonization of more pathogenic bacteria. Although both S. gordonii and macrophages are individually
important in periodontal disease progression, little is known about their interactions. We have found a novel, yet
counterintuitive, relationship between macrophages and S. gordonii where the bacterium is better able to survive
within, and promote enhanced cytokine release from macrophages with an inflammatory phenotype similar to
those present during disease. However, there remains a gap in the mechanistic understanding of oral
streptococcus-immune interactions with macrophages, and how changes in this interaction may contribute to the
ability of S. gordonii and/or macrophages to contribute to disease. The overall objective of this project is to
examine the mechanisms behind the observed immune consequences of S. gordonii interaction with
inflammatory macrophages. The central hypothesis is that S. gordonii perpetuates inflammation by
actively damaging macrophage phagosomes and activating the cytoplasmic inflammasome, a
subsequent pro-inflammatory response. To investigate this hypothesis this project aims to (1) define the
macrophage cellular mechanisms manipulated by S. gordonii to promote inflammatory response by
macrophages and (2) examine the acute responses of in vivo inflammatory macrophages responding to
S. gordonii. To achieve these aims a wide variety of techniques, from classical cell biology and biochemical
techniques to advanced microscopy, flow cytometry and animal models will be used. Completion of this project
will be a valuable step in understanding the dynamic interplay of commensals and the innate immune system
and how the two play a role in disease progression. It will also provide the investigator with diverse mentoring,
scientific and professional training, as further outlined in the proposal, to allow a successful transition to the next
stage of independently leading a successful research team.

## Key facts

- **NIH application ID:** 10023925
- **Project number:** 5F31DE029400-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Sarah Lucile Metcalfe
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,185
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023925

## Citation

> US National Institutes of Health, RePORTER application 10023925, Mechanisms of Oral Streptococcus Macrophage Activation (5F31DE029400-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10023925. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*