Immunoepidemiology of intestinal helminth infections. 4. Immunopathology in trichuriasis: lessons from the mouse model.

The severity and consequences of human Trichuris infection vary widely. This may reflect differences in immune response. T. muris is a natural parasite of mice which provides a close, well defined, easily manipulated model for otherwise uninvestigatable aspects of this response. Normal mice reject the parasite in 3 weeks, but mice subjected to transient immunosuppression around the time of infection develop a persistent caecal infection. Sequential histopathological studies have shown that infected, normal mice develop a marked intraepithelial, mucosal, 'globule leucocyte' response, accompanied by low-level lymphocytic and histiocytic responses in the lamina propria. The reaction is maximal at 3 weeks and declines towards normal after rejection. Infected, immunosuppressed mice show a slower response with, by weeks 4 and 5, fewer 'globule leucocytes', but a chronic colitis comprising heavy, mixed, mucosal and submucosal inflammation and crypt damage accompanied by persistent parasite infection. The 'globule leucocyte' has been characterized by cytochemistry and electron microscopy as having a mast cell origin. This study, with other evidence, suggests that the replacement of a Th2 (allergic) T helper cell response by a Th1 (cell-mediated) response may result in increased severity and persistence of colitis in response to Trichuris infection.