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Title: CRYPTOSPORIDIUM PARVUM INITIATES INFLAMMATORY BOWEL DISEASE IN GERMFREE T CELL RECEPTOR-ALPHA-DEFICIENT MICE

Author
item Sacco, Randy
item HAYNES, JOSEPH - IA STATE UNIV., AMES, IA
item Harp, James
item WATERS, W. - IA STATE UNIV., AMES, IA
item WANNEMUEHLER, MICHAEL - IA STATE UNIV., AMES, IA

Submitted to: American Journal of Pathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/22/1998
Publication Date: N/A
Citation: N/A

Interpretive Summary: Cryptosporidium parvum is a parasite that causes intestinal disease and diarrhea in economically important livestock species and in humans with AIDS. The disease is generally mild in individuals with a functional immune system but can be severe in individuals whose immune systems are not functioning properly. Laboratory mice with a defect in their immune system mhave been developed that are prone to intestinal disease with increasing age. In a prior study, we have shown that there is a more rapid development of intestinal disease when these mice are infected with C. parvum. Research from other laboratories has shown that these mice with a defect in their immune system do not develop intestinal disease if they are raised without intestinal organisms or exposure to environmental organisms (i.e., if they are germfree). It is not known whether one or more organisms are needed to initiate the intestinal disease in these animals. In this paper, we are the first to show that a single organism, C. parvum, can initiate the intestinal disease in these mice in the absence of any other microorganisms. We also show that these animals are less heavily infected with C. parvum if they have intestinal organisms than if they are raised under germfree conditions.

Technical Abstract: Flora-bearing mice with targeted disruption of T cell receptor (TCR)-alpha or beta genes spontaneously develop intestinal inflammation with features similar to ulcerative colitis in humans. TCR-alpha-deficient mice maintained germfree or colonized with a limited number of intestinal bacteria fail to develop inflammatory bowel disease (IBD)-like lesions. Evidently, inflammation in these mice does not develop spontaneously nor result from a generalized antigenic stimulation, but rather requires induction by a heretofore unidentified specific stimulus. We describe the development of IBD-like lesions in germfree TCR-alpha-deficient mice monoassociated with the protozoan Cyptosporidium parvum. Lesions were seen in distal ileum, cecum, and colon, and were most severe in the cecum. A prominent leukocytic infiltrate within the lamina propria was a common characteristic of the lesions observed in the C. parvum-infected germfree TCR-alpha-deficient mice. The leukocytic infiltrate was comprised of aggregates of B220**+ cells, the majority of which expressed sIgD (i.e., conventional B lymphocytes). It has been proposed that antigenic stimulation by a microorganism(s) is needed to initiate intestinal inflammation in TCR-alpha-deficient mice. Our results indicate that a single microoganism, C. parvum, is capable of triggering the development of IBD-like lesions in germfree TCR-alpha-deficient mice.