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 WBB6F1-W/W(v) (W/W(v)) and the control littermate WBB6F1+/+ (+/+) 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.
Furuta
Takahisa
T
Department of Microbiology and Immunology, Division of Infectious Genetics, University of Tokyo, Japan. furuta@ims.u-tokyo.ac.jp
Kikuchi
Takane
T
Iwakura
Yoichiro
Y
Watanabe
Naohiro
N
D000818:Animals; D000906:Antibodies / Q000009:adverse effects / Q000276:immunology / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008288:Malaria / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D051379:Mice; D008822:Mice, Transgenic; D010962:Plasmodium berghei / Q000502:physiology*; D051381:Rats; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha