TLR expression in bovine monocytes derived from cattle breeds with differing susceptibility to tropical theileriosis

Species: Ruminants Theileria annulata is an apicomplexan parasite of global economic importance. It is the causative agent of tropical theileriosis, which is a debilitating disease of cattle. It is spread by ticks of the Hyalomma species and covers areas from the Mediterranean basin to China. European cattle such as Holstein-Friesians ( Bos taurus ) are very susceptible to tropical theileriosis and the mortality rates amongst these breeds is between 40 and 90%. However, several breeds native to endemic areas, such as the Sahiwal cattle ( Bos indicus ) from Pakistan, are tolerant to the disease. T. annulata primarily infects bovine macrophages, which are reversibly transformed causing the macrophage and parasite to proliferate in synchrony. As a result of this transformation ex vivo cell lines, derived from experimental infection of cattle, have been grown in culture. Infection with T. annulata alters the function and phenotype of the macrophage, for example, the pathogen recognition receptor (PRR) CD14, which is involved in macrophage activation, is down-regulated. In order to better understand the roles of PRRs during infection with T. annulata we have investigated the expression of toll-like receptors (TLRs) in resting, activated and infected monocytes. Using ex vivo cell lines we have shown that all 10 TLRs are expressed during T. annulata infection and a correlation between pro-inflammatory cytokines and TLR expression has also been observed. A bovine macrophage-specific cDNA microarray has been constructed to investigate breed-specific differences in Sahiwal and Holstein monocytes during infection with T. annulata and after activation with lipopolysaccharide and interferon-?. Analysis of the microarray data showed a breed-specific difference in TLR10 expression during monocyte infection and activation. In Sahiwal macrophages TLR10 expression is up-regulated after infection and activation, while the Holstein macrophages slightly down-regulate TLR10 at the same time point. Additional studies are in progress to investigate further the importance of TLRs and pro-inflammatory cytokines and to elucidate further the roles they play during T. annulata infection.