title: Cross-reactive adaptive immune response to oral commensal bacteria results in an induction of receptor activator of nuclear factor-kappaB ligand (RANKL)-dependent periodontal bone resorption in a mouse model.
abstract: BACKGROUND
  The present study examined whether induction of an adaptive immune response to orally colonizing non-pathogenic Pasteurella pneumotropica by immunization with the phylogenetically closely related bacterium, Actinobacillus actinomycetemcomitans, can result in periodontal bone loss in mice.
  
  
  METHODS
  BALB/c mice harboring P. pneumotropica (P. pneumotropica(+) mice) in the oral cavity or control P. pneumotropica-free mice were immunized with fixed A. actinomycetemcomitans. The animals were sacrificed on day 30, and the following measurements were carried out: (i) serum immunoglobulin G and gingival T-cell responses to A. actinomycetemcomitans and P. pneumotropica; (ii) periodontal bone loss; and (iii) identification of receptor activator of nuclear factor-kappaB ligand (RANKL) -positive T cells in gingival tissue.
  
  
  RESULTS
  Immunization with A. actinomycetemcomitans induced a significantly elevated serum immunoglobulin G response to the 29-kDa A. actinomycetemcomitans outer membrane protein (Omp29), which showed strong cross-reactivity with P. pneumotropica OmpA compared to results in the control non-immunized mice. The A. actinomycetemcomitans-immunized P. pneumotropica(+) mice developed remarkable periodontal bone loss in a RANKL-dependent manner, as determined by the abrogation of bone loss by treatment with osteoprotegerin-Fc. The T cells isolated from the gingival tissue of A. actinomycetemcomitans-immunized P. pneumotropica(+) mice showed an in vitro proliferative response to both A. actinomycetemcomitans and P. pneumotropica antigen presentation, as well as production of soluble(s)RANKL in the culture supernatant. Double-color confocal microscopy demonstrated that the frequency of RANKL(+) T cells in the gingival tissue of A. actinomycetemcomitans-immunized P. pneumotropica(+) mice was remarkably elevated compared to control mice.
  
  
  CONCLUSIONS
  The induction of an adaptive immune response to orally colonizing non-pathogenic P. pneumotropica results in RANKL-dependent periodontal bone loss in mice.
authors.affiliation: Department of Immunology, The Forsyth Institute, Boston, MA 02115, USA. tkawai@forsyth.org
authors.forename: T
authors.initials: T
authors.lastname: Kawai
authors.forename: B J
authors.initials: BJ
authors.lastname: Paster
authors.forename: H
authors.initials: H
authors.lastname: Komatsuzawa
authors.forename: C W O
authors.initials: CW
authors.lastname: Ernst
authors.forename: R B
authors.initials: RB
authors.lastname: Goncalves
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.forename: K
authors.initials: K
authors.lastname: Ouhara
authors.forename: P P
authors.initials: PP
authors.lastname: Stashenko
authors.forename: M
authors.initials: M
authors.lastname: Sugai
authors.forename: M A
authors.initials: MA
authors.lastname: Taubman
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000276:immunology*; D016301:Alveolar Bone Loss / Q000276:immunology* / Q000382:microbiology*; D000818:Animals; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D003429:Cross Reactions; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D053244:Osteoprotegerin / Q000494:pharmacology; D044142:Pasteurella pneumotropica / Q000276:immunology* / Q000472:pathogenicity; D053245:RANK Ligand / Q000037:antagonists & inhibitors / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007074:Immunoglobulin G; C117494:Omp29 protein, Actinobacillus actinomycetemcomitans; D053244:Osteoprotegerin; D053245:RANK Ligand