Cryptosporidium parvum initiates inflammatory bowel disease in germfree T cell (receptor-alpha-deficient) mice

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 failed...

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Veröffentlicht in:The American journal of pathology 1998-12, Vol.153 (6), p.1717
Hauptverfasser: Sacco, Randy E, Haynes, Joseph S, Harp, James A, Waters, W Ray, Wannemuehler, Michael J
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container_issue 6
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container_title The American journal of pathology
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creator Sacco, Randy E
Haynes, Joseph S
Harp, James A
Waters, W Ray
Wannemuehler, Michael J
description 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 failed to develop inflammatory bowel disease (IBD)-like lesions. Evidently, inflammation in these mice does not develop spontaneously or 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 Cryptosporidium 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 composed of aggregates of B220+ cells, the majority of which expressed surface IgD (ie, 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 microbial species, C. parvum, is capable of triggering the development of IBD-like lesions in germfree TCR-alpha-deficient mice.
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title Cryptosporidium parvum initiates inflammatory bowel disease in germfree T cell (receptor-alpha-deficient) mice
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