Our previous studies have demonstrated that the alternative complement pathway and natural IgM antibodies play an important role in opsonization and phagocytosis of members of the Bacteroides fragilis group by neutrophils. Natural IgM antibodies act synergistically with the alternative pathway to facilitate adherence of the bacteria to neutrophils, which leads to ingestion and intracellular killing. The studies proposed in this application will extend these observations by determining the mechanisms by which natural IgM antibodies act synergistically with the alternative pathway to promote adherence of B. fragilis and B. thetaiotaomicron to neutrophils, the structural features of IgM required for this synergistic activity, the effects of natural IgM antibodies and the alternative pathway on activation of neutrophils, and the involvement of natural IgG antibodies in opsonization of these bacteria via the alternative pathway. Mechanisms responsible for the resistance of highly encapsulated isolates of the B. fragilis group to opsonization and phagocytosis by neutrophils will also be determined. These studies will increase our understanding of the role of natural antibodies and the alternative pathway in opsonization and phagocytosis of members of the B. fragilis group by neutrophils. Basic concepts resulting from this research may also be applicable to bacterial opsonization in general.