Murine Trypanosomiasis: Cellular Proliferation and Functional Depletion in the Blood, Peritoneum, and Spleen Related to Changes in Bone Marrow Stem Cells

Abstract

Previous reports have described profound effects on the function of the lymphoid system, especially the spleen, in mice infected with Trypanosoma brucei . This study provides further evidence of major change in the cell populations of the blood, peritoneum, and bone marrow, but shows that at least some of the stem cells of the bone marrow survive the damage caused by trypanosomes and retain their ability to repopulate the animal. In these infected mice the initial parasitemia was terminated by day 11 and was followed by a subpatent period of approximately 7 days before a final, lethal parasitemia occurred. Lymphopenia preceded the initial and final waves of parasites in the blood, and there was a marked increase in circulating neutrophils and large mononuclear cells for 1 week after the termination of the first wave of bloodstream parasitemia and during the final lethal parasitemia. Dividing macrophages were detected in the peritoneum only briefly during week 1 of infection, but the total number of peritoneal cells was increased from day 8 until the mice died. The bone marrow is severely stressed by the parasite infection. Total cell numbers and spleen colony-forming cells in the bone marrow were profoundly depleted during the resolution of the first parasitemia, but both these parameters largely recovered during the subpatent period before the mice were killed by the disease. Immune function was restored gradually after treatment with Berenil late in infection. We conclude that the progenitors of lymphocytes as well as the mature cells are affected by trypanosomes, but that some of the early bone marrow stem cells escape and rapidly repopulate the peripheral organs upon removal of the parasites.