Tumor necrosis factor alpha p55 receptor is important for development of memory responses to blood-stage malaria infection

Tumor necrosis factor alpha (TNF-alpha) is associated with malarial patholo gy in both humans and mice. In Plasmodium chabaudi chabaudi (AS) infections , the production of TNF-alpha and reactive metabolites from macrophages are also thought to play a role in controlling acute parasitemia. Since many o f the biological functions of TNF-alpha are effected through the p55 recept or (p55R), mice made defective in this receptor via a targeted gene disrupt ion (p55R(-/-)) have been used to study its involvement in the immune respo nse against P. chabaudi chabaudi and in the pathology associated with this infection. In the absence of the p55R, mice could overcome their primary in fection, although higher acute-blood-stage parasitemias and more significan t recrudescences were observed. Hypoglycemia, hypothermia, loss of erythroc ytes, and loss of body weight, which occur transiently in this infection, w ere exacerbated by the lack of the p55R, but the differences were small, su ggesting that other factors affect these symptoms. In contrast to wild-type (WT) mice, a second challenge infection in p55R(-/-) mice resulted in a co urse of infection similar to a primary infection. The malaria-specific immu noglobulin G antibody response of p55R(-/-) mice was lower than that of WT mice and was not increased by the second challenge infection. These data su ggest that p55R(-/-) mice do not develop an efficient memory B-cell respons e against malarial infection and that this antibody response is important i n immunity to reinfection.