| Autor: |
Chukkapalli SS; Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA., Ambadapadi S; Biodesign Institute, Arizona State University, Tempe, 727 E Tyler St 85287, AZ, USA., Varkoly K; Biodesign Institute, Arizona State University, Tempe, 727 E Tyler St 85287, AZ, USA., Jiron J; Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA., Aguirre JI; Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA., Bhattacharyya I; Department of Oral Diagnostic Sciences, College of Dentistry, University of Florida, Gainesville, FL 32610, USA., Morel LM; Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA., Lucas AR; Biodesign Institute, Arizona State University, Tempe, 727 E Tyler St 85287, AZ, USA., Kesavalu L; Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.; Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA. |
| Abstrakt: |
Plasma membrane-associated Toll-like receptor (TLR2 and TLR4) signaling contributes to oral microbe infection-induced periodontitis and atherosclerosis. We recently reported that either TLR2 or TLR4 receptor deficiency alters recognition of a consortium of oral pathogens, modifying host responses in periodontitis and atherosclerosis. We evaluated the effects of combined TLR2-/-TLR4-/- double knockout mice on innate immune signaling and induction of periodontitis and atherosclerosis after polybacterial infection with Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia and Fusobacterium nucleatum in a mouse model. Multispecies infections established gingival colonization in all TLR2-/-TLR4-/- mice and induced production of bacterial-specific IgG antibodies. In combined TLR2-/-TLR4-/- deficiency there was, however, reduced alveolar bone resorption and mild gingival inflammation with minimal migration of junctional epithelium and infiltration of inflammatory cells. This indicates a central role for TLR2 and TLR4 in periodontitis. Atherosclerotic plaque progression was markedly reduced in infected TLR2-/-TLR4-/- mice or in heterozygotes indicating a profound effect on plaque growth. However, bacterial genomic DNA was detected in multiple organs in TLR2-/-TLR4-/- mice indicating an intravascular dissemination from gingival tissue to heart, aorta, kidney and lungs. TRL2 and TLR4 were dispensable for systemic spread after polybacterial infections but TLR2 and 4 deficiency markedly reduces atherosclerosis induced by oral bacteria. |
