Optimal host resistance to microbial pathogens requires the selective activation of a particular cellular of humoral immune response. Delayed-type hypersensitivity responses medicated by Th1 cells are required to combat infection with obligate intracellular organisms, whereas Th2 cells are beneficial in infections with extracellular organisms, including oral pathogens. New immunization strategies developed by us and others show great promise in directing responses toward either a Th1 or Th2 phenotype. Infections of the dental pulp result in pulpal necrosis and the resorption of periapical bone. During the prior grant period, we found that pulpal infection elicits predominantly Th1-type pro-inflammatory responses, and that periapical bone resorption is dramatically inhibited by the endogenously expressed anti-inflammatory Th2 cytokine IL-10. In the proposed studies, we will test the hypothesis that these novel immunization strategies can be used to skew responses against the model organism P.gingivalis toward a Th2 phenotype, resulting in increased IL-10 expression and reduced periapical bone resorption.
In Aim 1, mouse strains that are genetically susceptible or resistant to P. gingivalis-induced periapical bone resorption will be identified. T cell lines from a resistant strain will be used to identify P.gingivalis antigens that preferentially stimulate IL-10 responses, using expression cloning (Aim 2).
Aim 3 will determine if immunization with P. gingivalis antigens can inhibit periapical bone resorption in vivo. The mechanism(s) by which P.gingivalis antigens induce IL-10 responses will be characterized in Aim 4. The goal of these studies is to devise new methods for immunomodulating proinflammatory pathways and bone resorption via preferential induction of IL-10.

National Institute of Health (NIH)
National Institute of Dental & Craniofacial Research (NIDCR)
Research Project (R01)
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Special Emphasis Panel (ZRG1-GRM (03))
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Shum, Lillian
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Forsyth Institute
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