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Cytokine induction by extracellular products of oral viridans group streptococci
H Takada1, Y Kawabata, M Tamura
1Department of Microbiology and Immunology, Kagoshima University Dental School, Japan.
Abstract:
During an etiological study of Kawasaki disease (mucocutaneous lymph node syndrome [MCLS]), we found that dominant viridans streptococcal strains on tooth surfaces and in the throat of both MCLS patients and non-MCLS control children formed erythrogenic and biologically active, extracellular products. In this study, we demonstrated that erythrogenic culture supernatant concentrates of representative strains (two Streptococcus mitis and two Streptococcus oralis), when injected intravenously, induced serum tumor necrosis factor alpha, interleukin-6 (IL-6), and gamma interferon in muramyldipeptide- or Propionibacterium acnes-primed C3H/HeN mice. The concentrates also induced tumor necrosis factor alpha, IL-6, and thymocyte-activating factor (essentially IL-1) in murine peritoneal macrophage, human monocyte, and human whole-blood cultures. An erythrogenic, heat-labile extracellular protein fraction (F-1) that was concentrated from the culture supernatants of a representative S. mitis strain exhibited the above-mentioned cytokine-inducing activity. This partially purified F-1 fraction also induced thymocyte-activating factor and IL-6 in human umbilical vascular endothelial cell and gingival fibroblast cultures.
Insights
Viridans streptococci from children with Kawasaki disease (mucocutaneous lymph node syndrome) produce extracellular products that induce inflammatory cytokines. A specific protein fraction (F-1) from these bacteria triggers immune responses in various cell types.
Area of Science:
- Microbiology
- Immunology
- Pediatric Disease Etiology
Background:
- Kawasaki disease (mucocutaneous lymph node syndrome) is a pediatric illness of unknown cause.
- Dominant viridans streptococcal strains in children, both with and without Kawasaki disease, produce extracellular products.
- These extracellular products are biologically active and erythrogenic.
Purpose of the Study:
- To investigate the biological activity of extracellular products from viridans streptococci.
- To determine if these products can induce cytokine production relevant to inflammatory responses.
- To identify potential etiological factors in Kawasaki disease.
Main Methods:
- Culture of Streptococcus mitis and Streptococcus oralis strains.
- Injection of concentrated culture supernatants into P. acnes-primed mice.
- Assay of cytokine levels (TNF-α, IL-6, IFN-γ, IL-1) in mouse serum and cell cultures (macrophages, monocytes, whole blood, endothelial cells, fibroblasts).
- Partial purification and characterization of an active extracellular protein fraction (F-1).
Main Results:
- Erythrogenic culture supernatant concentrates induced significant levels of tumor necrosis factor alpha, interleukin-6, and gamma interferon in mice.
- These concentrates also stimulated the production of tumor necrosis factor alpha, interleukin-6, and thymocyte-activating factor (IL-1) in murine and human cell cultures.
- A partially purified, heat-labile extracellular protein fraction (F-1) from Streptococcus mitis was responsible for the observed cytokine-inducing activity.
Conclusions:
- Extracellular products from dominant viridans streptococci strains possess potent cytokine-inducing properties.
- A specific protein fraction (F-1) from these bacteria can activate immune cells and induce key inflammatory cytokines.
- These findings suggest a potential role for viridans streptococcal products in the pathogenesis of Kawasaki disease.