title: Bacteria-reactive immune response may induce RANKL-expressing T cells in the mouse periapical bone loss lesion.
abstract: BACKGROUND
  The present study investigated whether bacteria infecting the root canal can activate any infiltrating T cells to produce receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL).
  
  
  METHODS
  Using a mouse model of periapical lesion induced by artificial dental pulp exposure, the presence of RANKL-positive T cells and osteoclasts in the periapical lesion was examined by an immunohistochemical approach. The bacteria colonizing the exposed root canal were identified by 16S ribosomal RNA (rRNA) sequence analysis. The isolated endodontic bacteria were further immunized to normal mice, and soluble activator of NF-κB ligand (sRANKL) production by the T cells isolated from the immunized mice was evaluated by ex vivo culture system.
  
  
  RESULTS
  RANKL-positive T cells along with TRAP+ osteoclasts were identified in periapical bone resorption lesions. The gram-negative bacterium Pasteurella pnumotropica, which was most frequently detected from the root canal of exposed pulp, showed remarkably elevated serum immunoglobulin G (IgG)-antibody response in pulp-exposed mice compared with control nontreated mice. Immunization of mice with P. pneumotropica induced not only serum IgG-antibody but also primed bacteria-reactive T cells that produced sRANKL in response to ex vivo exposure to P. pneumotropica.
  
  
  CONCLUSIONS
  T cells infiltrating the periapical region express RANKL, and the endodontic bacteria colonizing the root canal appear to induce RANKL expression from bacteria-reactive T cells, suggesting the possible pathogenic engagement of the immune response to endodontic bacteria in the context of developing bone resorptive periapical lesions.
authors.affiliation: Department of Immunology, The Forsyth Institute, Cambridge, Massachusetts, USA.
authors.forename: Marcelo J B
authors.initials: MJ
authors.lastname: Silva
authors.forename: Mikihito
authors.initials: M
authors.lastname: Kajiya
authors.forename: Emad
authors.initials: E
authors.lastname: AlShwaimi
authors.forename: Hajime
authors.initials: H
authors.lastname: Sasaki
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hong
authors.forename: Peter
authors.initials: P
authors.lastname: Ok
authors.forename: Taia M B
authors.initials: TM
authors.lastname: Rezende
authors.forename: Tom C
authors.initials: TC
authors.lastname: Pagonis
authors.forename: Robert R
authors.initials: RR
authors.lastname: White
authors.forename: Bruce J
authors.initials: BJ
authors.lastname: Paster
authors.forename: Philip
authors.initials: P
authors.lastname: Stashenko
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Kawai
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D016301:Alveolar Bone Loss / Q000276:immunology* / Q000382:microbiology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D015415:Biomarkers / Q000032:analysis; D017252:CD3 Complex / Q000276:immunology; D003786:Dental Pulp Cavity / Q000382:microbiology; D003789:Dental Pulp Exposure / Q000382:microbiology; D004195:Disease Models, Animal; D016983:Enterococcus / Q000276:immunology; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory / Q000276:immunology; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D010010:Osteoclasts / Q000473:pathology; D010326:Pasteurella Infections / Q000276:immunology*; D044142:Pasteurella pneumotropica / Q000145:classification / Q000276:immunology*; D010483:Periapical Diseases / Q000276:immunology* / Q000382:microbiology; D053245:RANK Ligand / Q000276:immunology*; D012329:RNA, Bacterial / Q000032:analysis; D012336:RNA, Ribosomal, 16S / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D000907:Antibodies, Bacterial; D015415:Biomarkers; D017252:CD3 Complex; D005456:Fluorescent Dyes; D007074:Immunoglobulin G; D007527:Isoenzymes; D053245:RANK Ligand; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; C505689:Tnfsf11 protein, mouse; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D016650:Fluorescein-5-isothiocyanate