Protective Roles of Mast Cells and Mast Cell-Derived TNF in Murine Malaria

Abstract

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 WBB6F1-W/Wv (W/Wv) and the control littermate WBB6F1+/+ (+/+) mice were infected with 1 × 105 of Plasmodium berghei ANKA. +/+ mice had lower parasitemia with higher TNF levels, as compared with W/Wv mice. Diminished resistance in W/Wv mice was considered to be due to mast cells and TNF. This fact was confirmed by experiments in W/Wv mice reconstituted with bone marrow-derived mast cells (BMMCs) of +/+ mice or of TNF−/− mice. W/Wv mice with BMMCs of +/+ mice exhibit lower parasitemia and mortality accompanying significantly higher TNF levels than those of W/Wv mice. Parasitemia in W/Wv 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/Wv mice reconstituted with BMMCs of +/+ mice as compared with W/Wv mice. These findings propose a novel mechanism that mast cells and mast cell-derived TNF play protective roles in malaria.