Monocytes from disease resistant and susceptible cattle display distinct transcriptome profiles during Theleiria annulata infection

The tick-borne protozoan parasite Theileria annulata causes a debilitating and often fatal disease of cattle called tropical theileriosis. The disease has a global economic impact on livestock production as it is endemic in many areas of the world from the Mediterranean basin to China. Control strategies have so far failed to eradicate T. annulata or its vector. An attractive alternative control strategy is to breed for combined resistance and productivity in cattle by using pre-existing genetic resistance. We have identified a Bos indicus breed of cattle that originates from Pakistan, the Sahiwal, which is resistant to tropical theileriosis. Our current studies aim to identify the genes underlying the resistance of Sahiwal cattle to T. annulata . T . annulata principally infects bovine macrophages and the pathology of the disease is associated with the intramacrophage stage of the parasite. Therefore we have focussed our studies on macrophages and monocytes derived from resistant (Sahiwal) and susceptible (Holstein-Friesian, B. taurus ) breeds of cattle. We have undertaken a global analysis of the transcriptional response of Sahiwal and Holstein-Friesian derived monocytes to T. annulata infection using a bovine macrophage specific microarray developed in our laboratory. This approach has identified over 60 expressed genes that exhibit breed-specific differential expression either in resting monocytes or during T. annulata infection, which may be related to T. annulata resistance. Many of the differentially expressed genes are cell-surface expressed proteins, e.g. prion protein and ICAM1, which are involved in the interaction of macrophages with other immune cells. Further analysis of the pathways leading to variation in expression of these molecules, may reveal the underlying causal genes for resistance and susceptibility to T. annulata , and provide new approaches for disease control.