During the course of infection with Trypanosoma brucei rhodesiense, the protozoa undergo frequent antigenic variations. The host responds by producing antibody to the predominant parasiste variants which are eliminated, most probably by cells of the mononuclear phagocytic system. One purpose of the research described here is to determine what role phagocytes play in eliminating trypanosomes from the blood of infected mice, and how their ability to phagocytose trypanosomes is affected by an ongoing infection. A second goal is to determine what effect modulation of phagocytosis has on trypanosomiasis. Finally, our third aim is to determine whether trypanosomiasis induces a generalized inhibition of phagocytosis, and how this might occur. Mice infected for varying lengths of time with cloned T.b. rhodesiense will be tested for their ability to clear radiolabeled trypanosomes from the blood. The trypanosome clone used to infect the mice, as well as clones derived from parasites arising later in infection, will be used in the clearance studies, both in the presence and absence of specific, exogenous antibody. Modulation of phagocytic function will be achieved by injections of specific antisera or nonspecific drugs. We will then evaluate the capacity of phagocytes to engulf and destroy the parasites, monitor the course of parasitemia, and ascertain lengths of survival compared with untreated, parasitized controls. The capacity of parasitized mice to contain the growth of Salmonella typhimurium will be used to monitor the nonspecific effects of trypanosomiasis of phagocytosis. We have found that trypanosomiasis rapidly destroys the capacity of mice to resist salmonellosis, and will determine if this is due to inability of the macrophages to phagocytose the bacteria, to impairment of intracellular killing, or to a suppression of antibody. With these studies, we hope to clarify the affects of infection on trypanosomiasis, and understand better how the parasites evade the effects of immunity.
| Jones, J F (1986) Trypanosoma rhodesiense: variable effects of cyclophosphamide on antibody production, survival, and parasitemia in infected mice. Exp Parasitol 61:261-9 |
