Impaired innate immune signaling due to combined Toll-like receptor 2 and 4 deficiency affects both periodontitis and atherosclerosis in response to polybacterial infection

Sasanka S. Chukkapalli, Sriram Ambadapadi, Kyle Varkoly, Jessica Jiron, Jose Ignacio Aguirre, Indraneel Bhattacharyya, Laurence M. Morel, Alexandra R. Lucas, Lakshmyya Kesavalu

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numberfty076
JournalPathogens and Disease
Volume76
Issue number8
DOIs
StatePublished - Nov 1 2018

Keywords

  • TLR2/TLR4 deficiency
  • atherosclerosis
  • innate immunity
  • oral bacteria
  • periodontitis
  • polybacterial infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology and Microbiology(all)
  • Microbiology (medical)
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Impaired innate immune signaling due to combined Toll-like receptor 2 and 4 deficiency affects both periodontitis and atherosclerosis in response to polybacterial infection'. Together they form a unique fingerprint.

Cite this