Transmissible ileal hyperplasia of hamsters. II. Ultrastructure.

The ultrastructure of developing ileal lesions was characterized in weanling hamsters with experimentally induced transmissible ileal hyperplasia (TIH). The primary lesion was mucosal hyperplasia with progressive replacement of mature villus columnar absorptive cells by undifferentiated crypt-type cells. The undifferentiated, mitotically active cells expanded onto villus walls from their normal location in crypts by Day 10 and reached villus tips by Day 14. Aggregates of slightly curved, 0.3 X 1.5 mu, rod-shaped bacteria were detected in the apical cytoplasm of crypt epithelium by Day ;. They replicated intracellularly and accumulated in progressively greater numbers in hyperplastic cells. Active penetration of cells by intralumenal bacteria was not seen. The appearance and distribution of TIH-associated antigen, demonstrated by indirect immunofluorescence, was identical to that observed for intracellular bacteria. Hyperplastic, bacteria-laden crypt epithelium penetrated adjacent supporting tissues. Dilated crypts with flattened epithelium ruptured and released organisms into surrounding tissues. Pyogranulomatous inflammation began at 17 to 25 days and preceded or accompanied penetration of the muscle layers by expanding crypts. Macrophages and neutrophils in inflammatory lesions contained many phagocytized bacteria. In some advanced lesions mature, bacteria-free absorptive cells and goblet cells reappeared. These observations support the hypothesis that intestinal bacteria cause TIH.