Research ArticleColitis

IL-22+ CD4+ T Cells Are Associated with Therapeutic Trichuris trichiura Infection in an Ulcerative Colitis Patient

Science Translational Medicine  01 Dec 2010:
Vol. 2, Issue 60, pp. 60ra88
DOI: 10.1126/scitranslmed.3001500

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It Wiggles and Jiggles and Tickles Inside

Although we all know that the old lady from the famed nursery rhyme swallowed the spider to catch the fly, no one knows why she swallowed the fly. We do know why the patient described in the study by Broadhurst et al. swallowed some worms—more specifically eggs of the helminth Trichuris trichiura—to treat his ulcerative colitis. What remains unknown are the root causes of ulcerative colitis, a form of inflammatory bowel disease. Now, Broadhurst et al. not only provide insight into the physiological effects of helminth infection on ulcerative colitis, they also glean some hints about potential targets for treating the underlying disease.

Ulcerative colitis is characterized by open sores or ulcers in the lining of the colon. The disease is associated with defects in immune regulation and is usually treated with immunosuppressive drugs. Parasitic worms, or helminths, modulate the immune response to survive within the guts of hosts. Because ulcerative colitis is more common in developed countries than in regions of the world with endemic helminth infections, researchers have proposed that ingestion of the worms may provide relief for colitis patients.

The study by Broadhurst et al. examines the potential mechanism that governs the relationship between parasitic whipworms and ulcerative colitis in a patient who ingested T. trichiura in lieu of other forms of treatment. They found that tissue that is actively affected by colitis has high numbers of immune cells that express the inflammatory cytokine interleukin-17 (IL-17) in the absence of the mucosal–healing cytokine IL-22. However, after helminth exposure, the disease went into remission, and IL-22–producing immune cells predominated. The authors then further profiled the molecular signals associated with ulcerative colitis in the presence and absence of helminth infection. This approach revealed that active ulcerative colitis is associated with an inflammatory signal, whereas helminth infection was associated with increased carbohydrate and steroid metabolism. These profiles suggest new targets for treating ulcerative colitis, although care must be taken because helminth infection sometimes results in an inflammatory response similar to that seen in inflammatory bowel disease. As with the old lady who swallowed the fly, we must be cautious that the treatment is not worse than the disease. No one wants to swallow a horse.

Footnotes

  • Citation: M. J. Broadhurst, J. M. Leung, V. Kashyap, J. M. McCune, U. Mahadevan, J. H. McKerrow, P. Loke, IL-22+ CD4+ T Cells Are Associated with Therapeutic Trichuris trichiura Infection in an Ulcerative Colitis Patient Sci. Transl. Med. 2, 60ra88 (2010).