METASTASIS OF THEILERIA-ANNULATA MACROSCHIZONT-INFECTED CELLS IN SCIDMICE IS MEDIATED BY MATRIX METALLOPROTEINASES

Theileria annulata (Ta)-infected leucocytes are able to disseminate in scid mice. The dose of virulent parasites of the Ta-Ode line required to achieve quantifiable dissemination was found to be 2 x 10(6) cells given i.p. Dissemination was higher on day 11 post-inoculation than o n day 18. The attenuated Ta-Ode cells were found to disseminate very p oorly compared to their virulent progenitors, which correlates with a marked reduction in matrix metalloproteinase (MMP) expression. A daily i.p. injection of mice with BB94, a synthetic inhibitor of MMPs, almo st completely ablated dissemination compared to controls. This provide s strong evidence that metastasis of Theileria annulata macroschizont- infected host cells is mediated by host MMPs induced by the parasite. This has important implications for explaining a number of pathologica l features of tropical theileriosis in cattle.