The role of the bone marrow in bovine trypanotolerance II. Macrophage function in Trypanosoma congolense-infected cattle

Sequential biopsies of sternal bone marrow (BM) of three trypanosusceptible Boran and three trypanotolerant N'Dama cattle were examined by light and t ransmission electron microscopy before and up to 112 days postinfection (DP I) with Trypanosoma congolense. Before infection, the percentage of cells o f the mononuclear phagocyte system (MPS) including the macrophage (M phi) a nd the calculated index of M phi volume in the BM were similar in both bree ds, whereas the mean Mg surface area was significantly higher (p<0.0001) in the Boran than in the N'Dama. During T. congolense infection, the MPS cell counts, the M phi surface area and the calculated M phi volume index incre ased significantly in both breeds particularly in the N'Dama. Macrophages phagocytosed only a few erythrocytes and mature neutrophils in both breeds before infection. During infection, M phi engulfed many erythro cytes, reticulocytes, normoblasts;, granulocytes and their precursors, and thrombocytes, as well as few lymphocytes and monocytes. Many M phi phagocyt osed cells from more than one cell lineage, and phagocytosis of nucleated c ells was preceded by attraction of the target cell and subsequent adhesion to the M phi suggesting a common mechanism of cell destruction. The M phi o f cattle maintained contact, through reciprocal U- or V-shaped microvilli o r filiform processes, with haemopoietic cells. These contacts increased dur ing the acute phase of T. congolense infection in both breeds and remained elevated in the N'Dama until 112 DPI, whereas they dropped to preinfection levels in the chronic phase (98, 112 DPI) in the Boran. Cumulatively, the absolute numbers, surface area, organelle contents and ca lculated volume index of the M phi, percentage of M phi with phagocytosed c ells, the total cells engulfed, adhesion of tar get cell to M phi prior to phagocytosis, phagocytosis of multiple cell lines, as well as the percentag e of M phi in contact with haemopoietic cells, and the total haemopoietic c ells in contact with M phi were significantly higher in the N'Dama than in the Boran. Cell phagocytosis and contact with haemopoietic cells decreased in Boran cattle during the chronic phase but remained elevated in the N'Dam a. The positive balance between the beneficial effects of M phi activation in the BM (enhanced haematopoiesis, and presumably parasite clearance and anti gen processing) and its deleterious effect (cytophagia) was greater in the trypanotolerant N'Dama than in the Boran, enabling the N'Dama to resist inf ection better. This study therefore demonstrates that superior BM responses , pivoted on vital M phi functions, play a major role in trypanotolerance.