Related Experiment Video
Updated: Jul 23, 2026
A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites
Published on: August 8, 2014
Global TLR2 and 4 deficiency in mice impacts bone resorption, inflammatory markers and atherosclerosis to
S S Chukkapalli1, I M Velsko1, M F Rivera-Kweh1
1Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL, USA.
Abstract:
Toll-like-receptors (TLRs) play a significant role in the generation of a specific innate immune response against invading pathogens. TLR2 and TLR4 signaling contributes to infection-induced inflammation in periodontal disease (PD) and atherosclerosis. Observational studies point towards a relationship between PD and atherosclerosis, but the role of TLR2 and TLR4 in the recognition of multiple oral pathogens and their modulation of host response leading to atherosclerosis are not clear. We evaluated the role of TLR2 and TLR4 signaling in the induction of both PD and atherosclerosis in TLR2-/- and TLR4-/- mice to polymicrobial infection with periodontal pathogens Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, and Fusobacterium nucleatum. Polybacterial infections have established gingival colonization in TLR2-/- and TLR4-/- mice and induction of a pathogen-specific immunoglobulin G immune response. But TLR deficiency dampened accelerated alveolar bone resorption and intrabony defects, indicating a central role in infection-induced PD. Periodontal bacteria disseminated from gingival tissue to the heart and aorta through intravascular dissemination; however, there was no increase in atherosclerosis progression in the aortic arch. Polybacterial infection does not alter levels of serum risk factors such as oxidized low-density lipoprotein, nitric oxide, and lipid fractions in both mice. Polymicrobial-infected TLR2-/- mice demonstrated significant levels (P < 0.05 to P < 0.01) of T helper type 2 [transforming growth factor-β1 , macrophage inflammatory protein-3α, interleukin-13 (IL-13)] and T helper type 17 (IL-17, IL-21, IL-22, IL-23) splenic T-cell cytokine responses. Increased heat-shock protein expression, hspa1a for Hsp 70, was observed for both TLR2-/- and TLR4-/- mice. This study supports a role for TLR2 and TLR4 in PD and atherosclerosis, corroborating an intricate association between two inflammatory diseases.
Insights
Toll-like receptors (TLR2 and TLR4) are crucial for periodontal disease (PD) and atherosclerosis. Their deficiency reduced PD but did not prevent bacterial spread or atherosclerosis, highlighting complex disease interactions.
Area of Science:
- Immunology
- Oral Biology
- Cardiovascular Research
Background:
- Toll-like receptors (TLRs), specifically TLR2 and TLR4, mediate innate immune responses to pathogens.
- Inflammation in periodontal disease (PD) and atherosclerosis is linked to TLR2 and TLR4 signaling.
- The precise role of TLRs in oral pathogen recognition and their contribution to atherosclerosis remains unclear.
Purpose of the Study:
- To investigate the roles of TLR2 and TLR4 in polymicrobial infection-induced PD and atherosclerosis.
- To evaluate the impact of TLR deficiency on host immune responses and disease progression.
Main Methods:
- Utilized TLR2 knockout (TLR2-/-) and TLR4 knockout (TLR4-/-) mice infected with key periodontal pathogens.
- Assessed PD markers, bacterial dissemination, atherosclerosis progression, serum risk factors, and splenic T-cell cytokine profiles.
- Measured heat-shock protein expression.
Main Results:
- TLR deficiency significantly reduced alveolar bone resorption and intrabony defects, indicating a key role in PD.
- Periodontal bacteria disseminated to the heart and aorta, but atherosclerosis progression in the aortic arch was not increased.
- Polymicrobial infection did not alter key serum risk factors for atherosclerosis.
- TLR2 deficiency modulated specific T helper type 2 and T helper type 17 splenic T-cell cytokine responses.
- Increased heat-shock protein (Hsp 70) expression was observed in both TLR2-/- and TLR4-/- mice.
Conclusions:
- TLR2 and TLR4 play critical roles in the pathogenesis of periodontal disease.
- While TLRs are involved in PD, their deficiency does not prevent bacterial dissemination or atherosclerosis progression.
- These findings support an intricate association between periodontal disease and atherosclerosis, mediated by TLR signaling pathways.
More Related Videos
08:34Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
09:51Screening Bioactive Nanoparticles in Phagocytic Immune Cells for Inhibitors of Toll-like Receptor Signaling
Published on: July 26, 2017
