Bos taurus and Bos indicus (Sahiwal) calves respond differently to infection with Theileria annulata and produce markedly different levels of acute phase proteins.

Disease-resistant livestock could provide a potentially sustainable and environmentally sound method of controlling tick and tick-borne diseases of livestock in the developing world. Advances in the knowledge and science of genomics open up opportunities to identify selectable genes controlling disease resistance but first, breeds and individuals with distinguishable phenotypes need to be identified. The Bos indicus breed, Sahiwal, has been exploited in dairy breeding programmes, because it is resistant to ticks and has relatively good performance characteristics compared to other indigenous cattle breeds of tropical regions. The analyses reported here show that Sahiwal calves were also more resistant than European Bos taurus (Holstein) dairy breed calves to tick-borne tropical theileriosis (Theileria annulata infection). Following experimental infection with T. annulata sporozoites, a group of Sahiwal calves all survived without treatment, with significantly lower maximum temperatures (P<0.01) and lower rates of parasite multiplication (P<0.05) than a group of Holstein calves, which all had severe responses. Although the Sahiwals became as anaemic as the Holsteins, other measures of pathology, including enlargement of the draining lymph node and the acute phase proteins, alpha1 acid glycoprotein and haptoglobin, were significantly less in the Sahiwals than in the Holsteins (P<0.05). Additionally, the Sahiwals had significantly lower resting levels of alpha1 acid glycoprotein than the Holsteins (P<0.05). Production of a third acute phase proteins, serum amyloid A, had very similar kinetics in both breeds. Acute phase proteins are produced in response to systemic release of the kinds of pro-inflammatory cytokines that are thought to be responsible for the pyrexic, cachectic and anorexic responses characteristic of tropical theileriosis. The prolonged production of alpha1 acid glycoprotein in the Holsteins is indicative of chronic production of circulating pro-inflammatory cytokines. In contrast, Sahiwals appear able to overcome infection with T. annulata as well as limit pathology by preventing the over-stimulation of pathways involving these cytokines.

The protozoan parasite, Theileria annulata, induces a distinct acute phase protein response in cattle that is associated with pathology.

Acute phase proteins (APP) are synthesised in the liver in response to the systemic presence of high levels of pro-inflammatory cytokines. Bacteria are considered to be strong inducers of APP whereas viruses are weak or non-inducers of APP. Very few reports have been published on APP induction by parasites. Here, we report that the tick-borne protozoan parasite of cattle, Theileria annulata, induced an atypical acute phase response in cattle. Following experimental infection, serum amyloid A (SAA) appeared first, followed by a rise in alpha(1) acid glycoprotein (alpha(1)AGP) in all animals, whereas haptoglobin, which is a major APP in cattle, only appeared in some of the animals, and generally at a low level. All three APP only became elevated around or after the appearance of schizonts in draining lymph nodes and after the first observed temperature rise. Increased alpha(1)AGP levels coincided with the appearance of piroplasms. The production of SAA and alpha(1)AGP correlated strongly with each other, and also with some clinical measures of disease severity including the time to fever, development of leucopaenia, parasitaemia and mortality. These results are consistent with the hypothesis that T. annulata causes severe pathology in susceptible cattle by inducing high levels of pro-inflammatory cytokines.

A dual role for immunosuppressor mechanisms in infection with Theileria annulata: well-regulated suppressor macrophages help in recovery from infection; profound immunosuppression promotes non-healing disease.

There is increasing evidence that immune mechanisms are involved in the pathogenesis of many parasitic infections, including infections with the tick-borne protozoan Theileria annulata. The initial stages of tropical theileriosis are characterised by the induction of a non-specific lymphoproliferation by schizont-infected cells which is believed to disrupt antigen recognition and interfere with protective immune responses. This study examined the possibility that cattle do not always succumb to infection because macrophages suppress this non-specific lymphoproliferation. The results provide evidence that lymphoproliferation in cattle may be controlled by two types of suppressor macrophages. The first type occurs in infected cattle and acts via a feedback loop well documented in other parasitic infections. This loop involves macrophages, apparently activated by high levels of gamma interferon produced by proliferating lymphocytes, which suppress lymphocyte proliferation via a prostaglandin-mediated pathway. The properties of a suppressor activity seen in immunised and challenged animals suggested that cattle also possess a type of novel suppressor macrophage recently described in filarial infections. This second type of suppressor macrophage does not seem to act via prostaglandin; its activity appeared to be linked to a suppressor epitope on the sporozoite antigen SPAG-1. Differences in the nature of the schizont-infected cells of the Friesian and Sahiwal calves used in one section of this work, in the in vitro and in vivo lymphoproliferative responses of the two groups of calves and in the behaviour of their suppressor macrophages suggested several reasons why the outcome of Theileria infections differed in the two cattle breeds. This study has extended our knowledge of the pluripotential activities of macrophages in T. annulata infections to include immunosuppression as well as anti-parasite responses and confirmed the view that the outcome of infection with T. annulata, as with many parasitic infections, depends upon the final balance of the protective and pathological properties of the immune system.