Deficiency in tumor necrosis factor alpha activity does not impair early protective Th1 responses against blood-stage malaria.
Blood-stage Plasmodium chabaudi AS infection was controlled by 4 weeks in mice with deletion of tumor necrosis factor p55 and p75 receptors (TNFR-knockout [KO]) and control wild-type (WT) mice, although female TNFR-KO mice showed slightly but significantly higher parasitemia immediately following the peak. Serum interleukin 12 (IL-12) p70 and gamma interferon (IFN-gamma) levels were similar but tumor necrosis factor alpha levels were significantly higher in TNFR-KO mice than in WT controls. Splenic IL-12 receptor beta1 and beta2 and IFN-gamma mRNA expression, as well as spleen cell production of IFN-gamma and IL-4, were comparable in both mouse types, but IL-10 production was significantly higher in cells from TNFR-KO mice than in cells from WT mice. Lipopolysaccharide-induced NO secretion by splenic macrophages in vitro was significantly reduced but systemic NO3- levels were similar in infected TNFR-KO and WT mice.
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McGill University Centre for the Study of Host Resistance and Montreal General Hospital Research Institute, Montreal, Quebec, Canada.
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Stevenson
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D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000097:blood / Q000235:genetics; D018664:Interleukin-12 / Q000097:blood; D008288:Malaria / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D018345:Mice, Knockout; D016788:Plasmodium chabaudi / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin / Q000235:genetics; D053707:Receptors, Interleukin-12; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D018417:Th1 Cells / Q000276:immunology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency*
D015703:Antigens, CD; D016207:Cytokines; C508440:Il12rb1 protein, mouse; C508443:Il12rb2 protein, mouse; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma