Cytokines and immunological control of Eimeria spp

Protozoan parasites belonging to the genus Eimeria cause considerable losses in livestock production in which stocking densities are high or environments restricted. The ability of hosts to mount immunological responses which limit parasite reproduction vary according to the particular species of Eimeria. Typically though, immune responses restrict parasite reproduction during primary infection and limit, if not prevent, subsequent infections. Although mechanisms of immunity are unknown, host immune responses have been exploited in the development of a method to control coccidiosis-immunisation with attenuated strains of Eimeria. Limitations of this control method, predominantly the cost of producing the attenuated parasites, necessitates identification of protective immune responses to facilitate selection of antigens for use in non-living vaccines. As in immune responses to many other parasitic infections of the gastrointestinal tract, the role of antibodies is at best minor, whereas T-cells are crucial. Numerous studies have shown that the intestinal mucosal T-cell population is dynamic; the number and phenotype of T-cells changes in response to Eimeria-infection. Specific changes in the intestinal T-cell population have not, however, been correlated with limitation of parasite reproduction. Experiments involving adoptive transfer of T-cell sub-populations and in vivo depletion of specific T-cells have shown that CD4+ T-cells and to a lesser extent CD8+ T-cells are important in immune responses which limit primary infection. In contrast, CD8+ T-cells are more important in subsequent infections with CD4+ T-cells having a lesser role. The effects of T-cells on Eimeria are partially mediated by the cytokines they release. Most attention has concentrated on interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) because these cytokines have been shown to limit other protozoan infections. IFN-gamma is produced in Eimeria-infected hosts but evidence that it is present at the site of infection is limited. Intestinal levels of IFN-gamma increase earlier in response to primary Eimeria-infection in mice which are relatively resistant, than in mice which are relatively susceptible. Neutralisation of endogenously produced IFN-gamma has shown that this cytokine limits oocyst production in either primary or secondary infections depending on the species of Eimeria. Production of TNF-alpha is also increased in infected hosts. In comparison with relatively susceptible mice, TNF-alpha is produced earlier and to a greater extent in the intestines of relatively resistant mice. Unexpectedly, injections of TNF-alpha into infected mice increased oocyst production. It remains to be determined whether the effects of endogenous TNF-alpha are the same as those of exogenous TNF-alpha. Mechanisms by which IFN-gamma and TNF-alpha modulate parasite reproduction have not been identified. A number of lines of experimentation have suggested that it is unlikely that IFN-gamma limits parasite reproduction through induction of the synthesis of reactive oxygen or reactive nitrogen intermediates, since both of these reactive intermediates have the capacity to exacerbate Eimeria-infection.