(Verbatim from application) Dentoalveolar abscess causing bacteria evade ingestion and destruction by phagocytic leukocytes and other local host immune mechanisms. If not promptly treated, these infections may rapidly spread along fascial planes, through lymphatics and via the bloodstream, resulting in significant morbidity and even mortality. Individuals with immunodeficiencies, or undergoing chemotherapy or immunosuppression, are particularly vulnerable. During the first grant period we developed a novel mouse model in which T and B cell deficient (SCID) mice with mixed anaerobic pulpal infections develop dentoalveolar abscesses, disseminating infections and sepsis. B cell deficient mice were also susceptible but with reduced frequence, whereas T cell deficient mice were resistant. Dissemination was partially prevented by passive transfer of antibody. In this application we will elucidate the mechanisms that govern protection vs susceptibility to these infections.
In Aim 1, the bacterial complexes that can cause disseminating infections in this model will be characterized.
Aim 2 will determine the mechanism(s) of antibody - and phagocytic leukocyte-mediated protection against pathogens.
In Aim 3, the mechanism(s) of increased susceptibility to disseminating infections and septic shock in SCID vs B cell deficient mice will be determined. The role of T cells and chemotactic cytokines in protection, or NK cells and shock-associated cytokines in increasing susceptibility will be determined in vivo. The goal of these studies is to fully define the immunological effector mechanisms that protect against disseminating dentoalveolar infections
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