Protective roles of mast cells and mast cell-derived TNF in murine malaria

TNF plays important roles in the protection and onset of malaria. Although mast cells are known as a source of TNF, little is known about the relationship between mast cells and pathogenesis of malaria. In this study, mast cell-deficient WBB6F(1)-W/W-v (W/W-v) and the control littermate WBB6F(1)(+/+) (+/+) mice were infected with 1 x 10(5) of Plasmodium berghei ANKA. +/+ mice had lower parasitemia with higher TNF levels, as compared with W/W-v mice. Diminished resistance in W/W-v mice was considered to be due to mast cells and TNF. This fact was confirmed by experiments in W/W-v mice reconstituted with bone marrow-derived mast cells (BMMCs) of +/+ mice or of TNF-/- mice. W/W-v mice with BMMCs of +/+ mice exhibit lower parasitemia and mortality accompanying significantly higher TNF levels than those of W/W-v mice. Parasitemia in W/W-v mice with BMMCs of TNF-/- mice was higher than that in +/+ mice. Activation of mast cells by anti-IgE or compound 48/80 resulted in release of TNF and decrease of parasitemia. In addition, splenic hypertrophy and increased number of mast cells in the spleen were observed after infection in +/+ mice and W/W-v mice reconstituted with BMMCs of +/+ mice as compared with W/W-v mice. These findings propose a novel mechanism that mast cells and mast cell-derived TNF play protective roles in malaria.