TY - JOUR
T1 - Global TLR2 and 4 deficiency in mice impacts bone resorption, inflammatory markers and atherosclerosis to polymicrobial infection
AU - Chukkapalli, S. S.
AU - Velsko, I. M.
AU - Rivera-Kweh, M. F.
AU - Larjava, H.
AU - Lucas, A. R.
AU - Kesavalu, L.
N1 - Funding Information:
This work was supported by NIH National Institute for Dental and Craniofacial Research NIDCR R01DE020820. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We acknowledge Dr Donghang Zheng for his assistance in histology tissue processing.
Publisher Copyright:
© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
KW - Fusobacterium nucleatum
KW - Porphyromonas gingivalis
KW - Tannerella forsythia
KW - Toll-like receptor-2-deficient mice
KW - Toll-like receptor-4-deficient mice
KW - Treponema denticola
KW - atherosclerosis
KW - periodontal disease
KW - polymicrobial infection
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U2 - 10.1111/omi.12165
DO - 10.1111/omi.12165
M3 - Article
C2 - 27224005
AN - SCOPUS:84978919497
SN - 2041-1006
VL - 32
SP - 211
EP - 225
JO - Molecular Oral Microbiology
JF - Molecular Oral Microbiology
IS - 3
ER -