Th1 immune response promotes severe bone resorption caused by Porphyromonas gingivalis.
Bacterial infections of the dental pulp result in soft tissue and alveolar bone destruction. It has been suggested that Th1 responses promote disease, whereas Th2 responses are protective. However, other studies have challenged this notion. To address this question, bone destruction was evaluated in mice immunized to develop strong and polarized Th1- or Th2-biased responses to the oral pathogen Porphyromonas gingivalis. Th1 bias was confirmed by the presence of high titers of serum IgG2a and the production of high levels of interferon (IFN)-gamma and no interleukin (IL)-4 by lymph node cells stimulated with P. gingivalis antigens. In contrast, Th2-biased animals had high titer IgG1 and no IgG2a, and their lymph node cells produced high levels of IL-4 but no IFN-gamma. Subsequent infection of the dental pulp with P. gingivalis caused extensive inflammation and alveolar bone destruction in Th1-biased mice, whereas Th2-biased mice and controls developed minimal lesions. Inflammatory granulomas in Th1-biased mice were heavily infiltrated with osteoclasts and had high local expression of IFN-gamma, IL-1alpha, and IL-1beta. Little or no IFN-gamma/IL-1alpha/IL-1beta and no obvious osteoclasts were detected in lesions of Th2-biased and control groups. These results directly demonstrate that specific Th1 responses promote severe infection-stimulated alveolar bone loss.
Stashenko
Philip
P
The Forsyth Institute, 140 The Fenway, Boston, MA 02115, USA.
Gonçalves
Reginaldo B
RB
Lipkin
Brad
B
Ficarelli
Alexander
A
Sasaki
Hajime
H
Campos-Neto
Antonio
A
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D016866:Bacteroidaceae Infections / Q000276:immunology* / Q000503:physiopathology; D001862:Bone Resorption / Q000276:immunology / Q000382:microbiology; D016207:Cytokines / Q000276:immunology; D007111:Immunity, Cellular; D007132:Immunoglobulin Isotypes / Q000276:immunology; D008213:Lymphocyte Activation; D008334:Mandible / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016966:Porphyromonas gingivalis; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
D000942:Antigens, Bacterial; D016207:Cytokines; D007132:Immunoglobulin Isotypes