The primary objective of this Center is to investigate the interplay between the immune system, the indigenous biota of infants and caries outcome. The proposed projects relate the interactions between the immune system and indigenous biota of the mother to those of the infant. By specifically examining those members of the indigenous biota associated with dental caries, as well as the role of the immune system in the colonization of these cariogens, we can gain insight into why some individuals manifest disease and others do not. An intervention trial will run parallel to a natural history study with the expectation that alterations in the mother's level of infection with mutans streptococci affects the acquisition and eventually, caries experience of the child. The target population for this proposal is comprised of African American families from Birmingham, Alabama. We confined our study to this group for two reasons: 1) African Americans have a higher prevalence and severity of caries than the general population. Outcomes from this research may help devise methods of preventing dental caries in this traditionally underserved segment of our population. 2) By constraining our study population, we will have more power for examining microbiological and immunological parameters by having less variation in the genetic composition of the study cohort. The Center will conduct studies relating to four possible avenues for preventing or altering the colonization of cariogenic bacteria: 1) prevention of transmission or maternal mutans streptococci (MS) to infants,, 2) basic and essential information as to the possibilities for developing a vaccine against dental caries, 3) the temporal acquisition of indigenous biota that may compete or augment the cariogenic potential of known cariogenic bacteria such as MS, and 4) devise prediction models based upon measured factors that might be useful in predicting children at risk prior to the onset of caries. Project 1 is the intervention trial mentioned above. Project 2 concerns itself with the questions as to ontogeny of the indigenous biota in infants and the source from whence they come. Project 3 documents the development of the infant's mucosal immune system in response to specific antigens as well as the effect of maternal immunoglobulins in shaping this responsiveness. Project 4 examines the role of the MHC genes and maternal 'imprinting' on the global immune response and explores 'self' vs. 'non-self' as it relates to the indigenous bacterial biota. An analytical/biostatistics, subject recruitment, sample procurement, and administrative core support the four Center projects. The broad, long-term objectives of this Center is to establish a consortium of both basic and applied scientists with the goal of solving clinical problems in humans. To do this, fundamental knowledge concerning the issues raised above must be first addressed. Much of the research proposed tests new paradigms and therefore, is basic. Nonetheless, the Center is clearly focused as to this basic information contributing to a clinical outcome.
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