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 have 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 lines results in their attenuation and this process is associated with alterations in both host and parasite gene expression. In particular, a loss in bovine MMP expression in later passage cultures suggests that these parasite-induced MMPs are virulence factors. As a means to further our understanding of the attenuation process we examine in detail the parasite-induced differential expression of one particular bovine proteinase, MMP9, in non-attenuated (p58) and attenuated (p158) passage levels of the Ode vaccine line. We show here that MMP9 expression is regulated at the transcriptional level and we suggest that a particular parasite-induced AP-1 recognition transcription factor present in the Ode non-attenuated line may have a role to play in the expression of this host gene. (C) 2000 Elsevier Science B.V. All rights reserved.