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-γ) levels were similar but tumor necrosis factor alpha levels were significantly higher in TNFR-KO mice than in WT controls. Splenic IL-12 receptor β1 and β2 and IFN-γ mRNA expression, as well as spleen cell production of IFN-γ 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 NO(3)(−) levels were similar in infected TNFR-KO and WT mice.