Studies on roles of mucosal mast cells in protection against intestinal parasites

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A repetitive i.p. injection of IL-3 induces mastocytosis which is 30-40% of the peak mastocytosis in Strongyloides ratti (Sr)-infection in C57BL/6 mice. Studies on mucosal mast cells (MMC) can be progressed by this finding. Expulsion of Sr was caused by two steps, from the small intestine to the caecum and from the caecum to outside. Although number of MMC in the caecum was increased by Sr-infection, numbers of eosinophils and goblet cells were also increased markedly in the caecum, suggesting a different effector mechanism is operating between the caecum and the small intestine. When nude mice were concurrently infected with Sr and N. brasiliensis (Nb) and injected repeatedly with IL-3, Sr was expelled but Nb was not. Therefore, mechanism of expulsion is distinct between Sr and Nb-infection. C57BL/6 mice injected repeatedly with more than a total of 10^4 U IL-3 and then infected with Sr showed strong protection against the worm in the small intestine. Induction of the effective protec … More tion by IL-3 injection took 4 to 5 days. The protective effect was well correlated with number of intestinal MMC increased. Mice injected with IL-3 and then orally infected with Sr began to eliminate the worms within 6 h post-infection. Therefore, the protection induced by IL-3 should have no concern with antigen specific immune responses. IL-3 injection could induce protection against not only larvae but also adult worms infected orally. However, it was ineffective to induce protection against tissue migrating larvae recovered from the head after s.c. infection. IL-3 injection could not induce protection against Sr in the mast cell deficient W/W^V mice. IL-3 injection increased amount of MMCP-1, a protease specific to MMC, in the intestinal lumen by 200 times and number of intestinal MMC in uninfected mice. MMC, therefore, can cause degranulation without IgE antibodies. All these results indicate that MMC are concerned with intestinal protection against Sr but not against Nb. Effector mechanisms of the worm expulsion should be different among various species of nematodes. Less