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Polymicrobial Oral Infection with Four Periodontal Bacteria Orchestrates a Distinct Inflammatory Response and Atherosclerosis in ApoE Mice.

Chukkapalli SS, Velsko IM, Rivera-Kweh MF, Zheng D, Lucas AR, Kesavalu L - PLoS ONE (2015)

Bottom Line: Periodontal microbiome infection is associated with significant decreases in Apoa1, Apob, Birc3, Fga, FgB genes that are associated with atherosclerosis.Periodontal infection for 12 weeks had modified levels of inflammatory molecules, with decreased Fas ligand, IL-13, SDF-1 and increased chemokine RANTES.In contrast, 24 weeks of infection induced new changes in other inflammatory molecules with reduced KC, MCSF, enhancing GM-CSF, IFNγ, IL-1β, IL-13, IL-4, IL-13, lymphotactin, RANTES, and also an increase in select inflammatory molecules.

View Article: PubMed Central - PubMed

Affiliation: Department of Periodontology, College of Dentistry, University of Florida, Gainesville, Florida, United States of America.

ABSTRACT
Periodontal disease (PD) develops from a synergy of complex subgingival oral microbiome, and is linked to systemic inflammatory atherosclerotic vascular disease (ASVD). To investigate how a polybacterial microbiome infection influences atherosclerotic plaque progression, we infected the oral cavity of ApoE mice with a polybacterial consortium of 4 well-characterized periodontal pathogens, Porphyromonas gingivalis, Treponema denticola, Tannerealla forsythia and Fusobacterium nucleatum, that have been identified in human atherosclerotic plaque by DNA screening. We assessed periodontal disease characteristics, hematogenous dissemination of bacteria, peripheral T cell response, serum inflammatory cytokines, atherosclerosis risk factors, atherosclerotic plaque development, and alteration of aortic gene expression. Polybacterial infections have established gingival colonization in ApoE hyperlipidemic mice and displayed invasive characteristics with hematogenous dissemination into cardiovascular tissues such as the heart and aorta. Polybacterial infection induced significantly higher levels of serum risk factors oxidized LDL (p < 0.05), nitric oxide (p < 0.01), altered lipid profiles (cholesterol, triglycerides, Chylomicrons, VLDL) (p < 0.05) as well as accelerated aortic plaque formation in ApoE mice (p < 0.05). Periodontal microbiome infection is associated with significant decreases in Apoa1, Apob, Birc3, Fga, FgB genes that are associated with atherosclerosis. Periodontal infection for 12 weeks had modified levels of inflammatory molecules, with decreased Fas ligand, IL-13, SDF-1 and increased chemokine RANTES. In contrast, 24 weeks of infection induced new changes in other inflammatory molecules with reduced KC, MCSF, enhancing GM-CSF, IFNγ, IL-1β, IL-13, IL-4, IL-13, lymphotactin, RANTES, and also an increase in select inflammatory molecules. This study demonstrates unique differences in the host immune response to a polybacterial periodontal infection with atherosclerotic lesion progression in a mouse model.

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Related in: MedlinePlus

Polybacterial-infection induced bacterial-specific humoral immune response and alveolar bone resorption.(A). Serum IgG antibody response to the four bacteria used in periodontal infection at 12 and 24 weeks. (B). Serum IgM antibody response to the four bacteria used in periodontal infection at 12 and 24 weeks. Representative left maxilla lingual view of polybacterial-infected and sham-infected mice at both 12- and 24 weeks with area of bone resorption outlined from alveolar bone crest to cementoenamel junction. (C). Total alveolar bone resorption is significantly greater than controls at 24 weeks of polybacterial infection. (D). Representative left maxilla lingual view of polybacterial-infected and sham-infected mice at both 12- and 24 weeks with area of bone resorption outlined from alveolar bone crest to cementoenamel junction. Poly—polybacterial infection, Con—sham-infected control, Pg/Td/Tf/Fn–polybacterial infection Pg–P. gingivalis, Td–T. denticola, Tf–T. forsythia, Fn–F. nucleatum. * p < 0.05, ** p < 0.01, *** p < 0.001.
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pone.0143291.g001: Polybacterial-infection induced bacterial-specific humoral immune response and alveolar bone resorption.(A). Serum IgG antibody response to the four bacteria used in periodontal infection at 12 and 24 weeks. (B). Serum IgM antibody response to the four bacteria used in periodontal infection at 12 and 24 weeks. Representative left maxilla lingual view of polybacterial-infected and sham-infected mice at both 12- and 24 weeks with area of bone resorption outlined from alveolar bone crest to cementoenamel junction. (C). Total alveolar bone resorption is significantly greater than controls at 24 weeks of polybacterial infection. (D). Representative left maxilla lingual view of polybacterial-infected and sham-infected mice at both 12- and 24 weeks with area of bone resorption outlined from alveolar bone crest to cementoenamel junction. Poly—polybacterial infection, Con—sham-infected control, Pg/Td/Tf/Fn–polybacterial infection Pg–P. gingivalis, Td–T. denticola, Tf–T. forsythia, Fn–F. nucleatum. * p < 0.05, ** p < 0.01, *** p < 0.001.

Mentions: To confirm generation of immune response against periodontal bacteria, serum IgG and IgM antibody response to each of the infecting bacteria was determined in infected and control mice at 12 and 24 weeks of infection. Infected mice demonstrated significant serum IgG titers (p < 0.01–0.001) against all 4 bacteria relative to sham-infected controls at 12 weeks of infection, and to P. gingivalis, T. forsythia and F. nucleatum at 24 weeks of infection (p < 0.001) (Fig 1A). The IgM response to P. gingivalis, T. forsythia, and F. nucleatum was significant in 12 week infected mice (p < 0.05–0.001) relative to sham-infected mice, while the 24 week IgM response was significant for P. gingivalis (p < 0.001) and T. forsythia (p < 0.01) (Fig 1B).


Polymicrobial Oral Infection with Four Periodontal Bacteria Orchestrates a Distinct Inflammatory Response and Atherosclerosis in ApoE Mice.

Chukkapalli SS, Velsko IM, Rivera-Kweh MF, Zheng D, Lucas AR, Kesavalu L - PLoS ONE (2015)

Polybacterial-infection induced bacterial-specific humoral immune response and alveolar bone resorption.(A). Serum IgG antibody response to the four bacteria used in periodontal infection at 12 and 24 weeks. (B). Serum IgM antibody response to the four bacteria used in periodontal infection at 12 and 24 weeks. Representative left maxilla lingual view of polybacterial-infected and sham-infected mice at both 12- and 24 weeks with area of bone resorption outlined from alveolar bone crest to cementoenamel junction. (C). Total alveolar bone resorption is significantly greater than controls at 24 weeks of polybacterial infection. (D). Representative left maxilla lingual view of polybacterial-infected and sham-infected mice at both 12- and 24 weeks with area of bone resorption outlined from alveolar bone crest to cementoenamel junction. Poly—polybacterial infection, Con—sham-infected control, Pg/Td/Tf/Fn–polybacterial infection Pg–P. gingivalis, Td–T. denticola, Tf–T. forsythia, Fn–F. nucleatum. * p < 0.05, ** p < 0.01, *** p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664240&req=5

pone.0143291.g001: Polybacterial-infection induced bacterial-specific humoral immune response and alveolar bone resorption.(A). Serum IgG antibody response to the four bacteria used in periodontal infection at 12 and 24 weeks. (B). Serum IgM antibody response to the four bacteria used in periodontal infection at 12 and 24 weeks. Representative left maxilla lingual view of polybacterial-infected and sham-infected mice at both 12- and 24 weeks with area of bone resorption outlined from alveolar bone crest to cementoenamel junction. (C). Total alveolar bone resorption is significantly greater than controls at 24 weeks of polybacterial infection. (D). Representative left maxilla lingual view of polybacterial-infected and sham-infected mice at both 12- and 24 weeks with area of bone resorption outlined from alveolar bone crest to cementoenamel junction. Poly—polybacterial infection, Con—sham-infected control, Pg/Td/Tf/Fn–polybacterial infection Pg–P. gingivalis, Td–T. denticola, Tf–T. forsythia, Fn–F. nucleatum. * p < 0.05, ** p < 0.01, *** p < 0.001.
Mentions: To confirm generation of immune response against periodontal bacteria, serum IgG and IgM antibody response to each of the infecting bacteria was determined in infected and control mice at 12 and 24 weeks of infection. Infected mice demonstrated significant serum IgG titers (p < 0.01–0.001) against all 4 bacteria relative to sham-infected controls at 12 weeks of infection, and to P. gingivalis, T. forsythia and F. nucleatum at 24 weeks of infection (p < 0.001) (Fig 1A). The IgM response to P. gingivalis, T. forsythia, and F. nucleatum was significant in 12 week infected mice (p < 0.05–0.001) relative to sham-infected mice, while the 24 week IgM response was significant for P. gingivalis (p < 0.001) and T. forsythia (p < 0.01) (Fig 1B).

Bottom Line: Periodontal microbiome infection is associated with significant decreases in Apoa1, Apob, Birc3, Fga, FgB genes that are associated with atherosclerosis.Periodontal infection for 12 weeks had modified levels of inflammatory molecules, with decreased Fas ligand, IL-13, SDF-1 and increased chemokine RANTES.In contrast, 24 weeks of infection induced new changes in other inflammatory molecules with reduced KC, MCSF, enhancing GM-CSF, IFNγ, IL-1β, IL-13, IL-4, IL-13, lymphotactin, RANTES, and also an increase in select inflammatory molecules.

View Article: PubMed Central - PubMed

Affiliation: Department of Periodontology, College of Dentistry, University of Florida, Gainesville, Florida, United States of America.

ABSTRACT
Periodontal disease (PD) develops from a synergy of complex subgingival oral microbiome, and is linked to systemic inflammatory atherosclerotic vascular disease (ASVD). To investigate how a polybacterial microbiome infection influences atherosclerotic plaque progression, we infected the oral cavity of ApoE mice with a polybacterial consortium of 4 well-characterized periodontal pathogens, Porphyromonas gingivalis, Treponema denticola, Tannerealla forsythia and Fusobacterium nucleatum, that have been identified in human atherosclerotic plaque by DNA screening. We assessed periodontal disease characteristics, hematogenous dissemination of bacteria, peripheral T cell response, serum inflammatory cytokines, atherosclerosis risk factors, atherosclerotic plaque development, and alteration of aortic gene expression. Polybacterial infections have established gingival colonization in ApoE hyperlipidemic mice and displayed invasive characteristics with hematogenous dissemination into cardiovascular tissues such as the heart and aorta. Polybacterial infection induced significantly higher levels of serum risk factors oxidized LDL (p < 0.05), nitric oxide (p < 0.01), altered lipid profiles (cholesterol, triglycerides, Chylomicrons, VLDL) (p < 0.05) as well as accelerated aortic plaque formation in ApoE mice (p < 0.05). Periodontal microbiome infection is associated with significant decreases in Apoa1, Apob, Birc3, Fga, FgB genes that are associated with atherosclerosis. Periodontal infection for 12 weeks had modified levels of inflammatory molecules, with decreased Fas ligand, IL-13, SDF-1 and increased chemokine RANTES. In contrast, 24 weeks of infection induced new changes in other inflammatory molecules with reduced KC, MCSF, enhancing GM-CSF, IFNγ, IL-1β, IL-13, IL-4, IL-13, lymphotactin, RANTES, and also an increase in select inflammatory molecules. This study demonstrates unique differences in the host immune response to a polybacterial periodontal infection with atherosclerotic lesion progression in a mouse model.

Show MeSH
Related in: MedlinePlus