Experimental chronic infection induced in mice by Actinomyces israelii entrapped in alginate gel

Tissue responses to experimentally induced actinomycotic lesions were investigated in mice by both light and transmission electron microscopy. Micro-organisms of Actinomyces israelii were entrapped in alginate gel and injected into the subcutaneous tissue over the periosteum of the mouse cranium. One day after the injection (initial stage), a non-stained amorphous structure was located in the core of the lesion, corresponding to the injected gel with bacteria. Numerous neutrophils surrounded the core region and phagocytized the injected complex actively. At days 3–7 (intermediate stage), the lesion became well developed. The core structure became eosinophilic and separated to form island-like structures. No lesion was recognized in the control group (gel without bacteria) until day 14. After 30 days (late stage), the lesions displayed more static features, similar to the “sulphur granules” characteristic of actinomycotic lesions. At the late stage, foamy cells increased in number and took the place of neutrophils in the alginate islands. By transmission electron microscopy these foamy cells were seen to be filled with lysosomal vesicles containing electron-dense foreign material. Thus, these cells appeared to be macrophages that had phagocytized degenerated neutrophils containing bacteria. Along with the active phagocytosis by foamy cells that progressed in the late stage, a collagenous capsule became conspicuous and separated the lesion from the intact tissue. The bacteria remained in the gel islands until at least day 60, although they considerably decreased in number with time. Serum IgG antibody titres began to rise within 24 h of the injection, reached a peak concentration at day 14 and remained a significantly high (p<0.01, vs 0 time) until day 120. These results suggest that this animal model is useful for inducing experimental chronic infectious lesions.