Interaction of African trypanosomes with the immune system

Abstract

African trypanosomes cause disease in man and domestic animals. The parasites have the ability to escape immune control by two means: by antigenic variation of the surface glycoprotein coat so that waves of variant parasites arise and by inducing a general immunosuppression affecting immune responses to the parasite as well as to parasite-unrelated antigens. The cellular basis of the immune dysfunction will be discussed in relation to a mouse model system - it is the result of proliferative stimuli to T- or B-cells which then become refractory to selection by antigen and normal control signals. Recent experiments have focused on macrophages as important direct target cells for parasite action. We have obtained no evidence for a parasite derived mitogen acting directly on B- or T-cells. In vitro cell proliferation is associated with accessory cells and relates only to T-cells. During infection, macrophages become activated with changes in receptor expression and mediator release, so that there is, for example, spontaneous IL-1 release (with a role in T- and possibly in B-cell proliferation) and several-fold increases in PGE2 secretion, with its immunosuppressive activities. We also find parasitaemia-associated release of alpha-beta and gamma interferon by various cells which in turn influences immune function. The active parasite component is associated with parasite membranes, but its nature has not been further defined. We proposed that the macrophage changes provide a general pathway causing immune dysfunction associated with many infections, be they parasitic or caused by other invading organisms.