Loss of matrix metalloproteinase 9 activity in Theileria annulata-attenuated cells is at the transcriptional level and is associated with differentially expressed AP-1 species

The schizont stage of the protozoan parasite Theileria annulata reversibly transforms bovine monocytes into an immortalised and metastatic state. We h ave been studying T. annulata induction of host matrix metalloproteinases ( MMP) which are involved in parasite dissemination and pathogenesis. We have observed that prolonged in vitro culture of T. annulata-infected cell line s results in their attenuation and this process is associated with alterati ons in both host and parasite gene expression. In particular, a loss in bov ine MMP expression in later passage cultures suggests that these parasite-i nduced MMPs are virulence factors. As a means to further our understanding of the attenuation process we examine in detail the parasite-induced differ ential expression of one particular bovine proteinase, MMP9, in non-attenua ted (p58) and attenuated (p158) passage levels of the Ode vaccine line. We show here that MMP9 expression is regulated at the transcriptional level an d we suggest that a particular parasite-induced AP-1 recognition transcript ion factor present in the Ode non-attenuated line may have a role to play i n the expression of this host gene. (C) 2000 Elsevier Science B.V. All righ ts reserved.