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Virulence. 2018;9(1):1263-1272.

Treponema denticola enolase contributes to the production of antibodies against ENO1 but not to the progression of periodontitis.

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제1저자 이아름 · 교신저자 송영욱

PMID 30001173 PMC6104692 DOI 10.1080/21505594.2018.1496775 IF 6.8 류마티스내과
소속 (5)
  1. a Department of Immunology and Molecular Microbiology, School of Dentistry and Dental Research Institute , Seoul National University , Seoul , Korea.
  2. b Department of Periodontology, School of Dentistry and Dental Research Institute , Seoul National University , Seoul , Korea.
  3. c Department of Preventive and Social Dentistry, School of Dentistry , Seoul National University.
  4. d Department of Internal Medicine , Seoul National University Hospital.
  5. e Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and College of Medicine , Seoul National University , Seoul , Korea.

Abstract

Autoantibodies against alpha-enolase (ENO1) are often detected in various infectious and autoimmune diseases. Anti-ENO1 antibody titers were reported to be associated with the severity of periodontitis in patients with rheumatoid arthritis. Because the enolase of the periodontal pathogen Treponema denticola (TdEno) has the highest homology with ENO1 among the enolases of human-associated bacteria, we hypothesized that anti-ENO1 autoantibodies produced during the immune response to TdEno may contribute to the progression of periodontitis and tested it in human and mouse systems. In human subjects with healthy periodontium or chronic periodontitis, a strong positive correlation between the levels of anti-TdEno and anti-ENO1 antibodies was observed. In addition, the purified anti-TdEno antibodies recognized ENO1 as well as TdEno in a dot blot, confirming the cross-reactivity between TdEno and ENO1. However, anti-ENO1 antibody titers were not associated with the severity of periodontitis. To further investigate the role of TdEno in the production of anti-ENO1 antibodies and the progression of periodontitis, mice received an oral gavage of P. gingivalis alone, subcutaneous immunization with TdEno alone, or both P. gingivalis oral gavage and TdEno immunization. Immunization with TdEno induced not only anti-TdEno but also anti-mouse Eno1 (mEno1) antibodies and increased the expression of TNFα in the gingival tissues. However, alveolar bone loss was not increased by TdEno immunization. In conclusion, autoreactive anti-ENO1/mEno1 antibodies that are produced as byproducts during the antibody response to TdEno play a minimal role in the progression of periodontitis in the absence of rheumatoid arthritis.

Keywords

TNFαTreponema denticolaautoantibodyenolaseperiodontitis

Figures

Figure 1.
Figure 1. The homology of TdEno with ENO1 and mEno1. (a) The amino acid sequences of ENO1, mEno1, and TdEno were aligned. Compared with ENO1, identical and conserved amino acids are highlighted in dark and light grey, respectively. B cell epitopes predicted using the Emini Surface Accessibility Prediction method in each protein were marked with red squares. The epitopes of ENO1 and TdEno located at the overlapping regions of aligned sequences are labeled from E1 to E7. (b) The seven epitopes are highlighted in yellow at the known structure (PDB 3B97) of ENO1 (left panel). To confirm the reliability of structure homology modeling, the structure of ENO1 was constructed at the SWISS-MODEL server using the PDB 3B97 as a template (middle panel). The structure homology of TdEno with ENO1 is shown in the right panel.
Figure 2.
Figure 2. The cross-reactivity of anti-TdEno antibodies with ENO1 in human subjects (a) Concentrations of anti-TdEno and anti-ENO1 IgG antibodies in sera from subjects with slight (sPD) or moderate (mPD) chronic periodontitis were determined by ELISA. (b) Spearman’s correlation between the levels of anti-TdEno and anti-ENO1 antibodies is shown. (c) Various amounts of recombinant TdEno and ENO1 proteins, the lysate and culture supernatant of T. denticola, and the lysates of human cell lines (THP-1 and HOK-16B) were subjected to dot blotting using anti-TdEno antibodies that were affinity-purified from the pooled sera.
Figure 3.
Figure 3. The effect of TdEno-induced anti-mEno1 antibodies on the progression of periodontitis in mice (a) The experimental scheme is shown. (b) Concentrations of anti-TdEno, anti-mEno1, and anti-ENO1 IgG antibodies in mouse sera were determined by ELISA. (c) Spearman’s correlation between the levels of anti-TdEno and either anti-mEno1 or anti-ENO1 antibodies is shown. (d) Images of the maxillary first molar of a representative mouse from each group are shown. Distances between the cemento-enamel junction (CEJ) and alveolar bone crest (ABC) at four lingual sites per the first molar were measured (left panel). The mean value for each mouse was graphed (right panel). The horizontal line presents the mean of each group. *p < 0.05 and **p < 0.005, compared to sham, †p < 0.0001, compared to Pg, and ǂp < 0.05 and ǂǂp < 0.05, compared to TdEno.
Figure 4.
Figure 4. Expression of inflammatory cytokines in the gingival tissues (a) Expression levels of TNFα and IL-1β mRNA in the gingival tissues were measured by real-time PCR. *p < 0.05 and **p < 0.005, compared to sham. (b) Spearman’s correlations between TNFα and alveolar bone loss, anti-mEno1 antibodies and TNFα or alveolar bone loss are shown.

그림 출처: PubMed Central 공개 논문 (PMC6104692)

그 밖의 정보
출판 형태
Journal Article, Research Support, Non-U.S. Gov't
저널
Virulence · eISSN 2150-5608
MeSH
Adult · Aged · Animals · Antibodies, Bacterial / blood · Arthritis, Rheumatoid · Autoantibodies / blood · Biomarkers, Tumor / immunology · Chronic Periodontitis / microbiology · DNA-Binding Proteins / immunology · Disease Progression · Female · Gingiva / immunology / microbiology · Humans · Immunization · Male · Mice · Middle Aged · Phosphopyruvate Hydratase / immunology · Porphyromonas gingivalis · Treponema denticola / enzymology / immunology · Tumor Necrosis Factor-alpha / genetics · Tumor Suppressor Proteins / immunology
Substances
Antibodies, Bacterial · Autoantibodies · Biomarkers, Tumor · DNA-Binding Proteins · Tumor Necrosis Factor-alpha · Tumor Suppressor Proteins · ENO1 protein, human · Phosphopyruvate Hydratase
참고문헌
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