Impaired innate immune signaling due to combined Toll-like receptor 2 and 4 deficiency affects both periodontitis and atherosclerosis in response to polybacterial infection.
Open accessAbstract
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.
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DNA from oral microbes can be transmitted from the gingival tissue to the pulmonary vasculature.
“Besides colonizing the lungs themselves, DNA from oral microbes can be transmited from the gingival tissue to the pulmonary vasculature (Chukkapalli et al., 2018), this might be a form of distant dissemination causing lung diseases.”
From Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection (2020) · cites this paper as Chukkapalli et al., 2018
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Cited by
Sorted by citations
Oral Microbiome and SARS-CoV-2: Beware of Lung Co-infection
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- Authors
- Chukkapalli, S. S., Ambadapadi, S., Varkoly, K., Jiron, J., Aguirre, J. I., Bhattacharyya, I., Morel, L. M., Lucas, A. R., & Lakshmyya, K.
- Affiliations
- University of Florida (US)
- Arizona State University (US)
- Department of Periodontology, College of Dentistry, University of Florida, Gainesville, FL 32610, USA
- ORCID
- Venue
- Pathogens and Disease
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-10-23
- Volume
- 76
- Issue
- 8
- ISSN
- 2049-632X (ISSN-L)
- PMC
- PMC6251349
- OpenAlex
- W2898502968
- Cited by
- 30
- References
- 42
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 5 · 2020: 3 · 2019: 1
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (am)
- Locations
- Pathogens and Disease (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Dental and Craniofacial Research (R01DE020820)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- TLR2, TLR4, periodontitis, atherosclerosis, oral pathogens, Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia, Fusobacterium nucleatum, innate immune signaling, alveolar bone loss, gingivitis, atherosclerotic plaque
- MeSH terms
- Tannerella forsythia, Animals, Animal Structures, Bacterial Infections, Female, Immunity, Innate, Male, Periodontitis, Signal Transduction, Porphyromonas gingivalis, Fusobacterium nucleatum, Mice, Knockout, Treponema denticola, Atherosclerosis, Toll-Like Receptor 2, Toll-Like Receptor 4, Coinfection
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