SIGNAL-TRANSDUCTION IN HOST-CELLS MEDIATED BY GLYCOSYLPHOSPHATIDYLINOSITOLS OF THE PARASITIC PROTOZOA, OR WHY DO THE PARASITIC PROTOZOA HAVE SO MANY GPI MOLECULES

Considerable circumstantial evidence indicates that glycosylphosphatid ylinositol (GPI) molecules of mammalian origin are able to mediate sig nal transduction in lymphoid cells. For example, perturbation of GPI-a nchored surface proteins, but not transmembrane forms of these molecul es, can lead to the activation of T lymphocytes. GPIs appear also to b e precursors of pharmacologically active phosphoinositol-glycans which mediate responses to hormones such as insulin, nerve growth factor an d IL-2. Nonetheless, the biochemical mechanisms of signal transduction by GPIs remain obscure. We have shown that structurally defined GPIs of protozoal parasite origin are able to mediate signal transduction i n host macrophages and lymphocytes, by substituting for the putative e ndogenous GPI-based signalling mechanisms of the host. Signalling by p arasite GPIs appears to involve the activation of protein tyrosine kin ase and protein kinase C. Evidence from other sources indicates that s tructurally variant GPIs may provide anergic signals to down-regulate host cell function. These phenomena may represent mechanisms by which eukaryotic parasites regulate host cell function, and can explain a va riety of pathological and immunological features of protozoal infectio ns. Furthermore, protozoal GPIs may prove to be an informative model s ystem for the analysis of GPI-mediated signal transduction in lymphocy tes and macrophages.