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.