We have demonstrated that gonococci causing disseminated infection (DGI) stimulate neutrophil (PMN) chemotaxis less efficiently and are opsonized and ingested less readily than gonococci isolated from patients with symptomatic uncomplicated local infection. These differences may relate to the pathogenesis of dissemination and may help to explain the paucity of genital symptoms in patients with DGI. Differences in the interaction of DGI and local strains with complement and with immunoglobulins present in different human sera account for the alternative expressions in models of the host response. In particular, differences between these strains with respect to complement-dependent serum bactericidal activity, chemotaxis and opsonization in normal serum are not reflections of differences in complement consumption by, or fixation to, these organisms. Instead, the different behavior of these two types of gonococci in the model systems appears to be due to the lack of, or muted functional expression of, complement bound to the DGI strains. We postulate that ineffective functional expression of complement bound to DGI strains may be related to two factors: the effect of blocking antibody and the site of complement binding. The focus of this proposal is the interaction of complement with Neisseria gonorrhoeae. This interaction has three basic overlapping components: complement, antigonococcal antibody and gonococcal antigens. We seek to characterize the interplay of these three factors for different clinical gonococcal isolates in different sera by correlating binding studies with functional expression in the in vitro models of host response. In addition, we will continue our studies on the association between genetic deficiencies of the terminal complement components and systemic Neisseria infection. We anticipate that the results of the proposed experiments will: 1) enhance our understanding of the pathogenesis of both local and disseminated gonococcal infection; 2) provide an understanding of the mechanism(s) that account for the ineffective functional expression of complement components bound to the surface of DGI strains; and 3) be valuable for decisions regarding preventive or therapeutic intervention in gonococcal infection.
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