Role of interferon-gamma and tumor necrosis factor in host resistance to Plasmodium chabaudi AS.
The contribution of the T cell- and macrophage-derived cytokines, interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF), respectively, in the cell-mediated mechanisms leading to acquired immunity to blood-stage Plasmodium chabaudi AS was investigated. To examine the contribution of IFN-gamma, resistant C57BL-derived mice were treated during infection with two different neutralizing, anti-murine IFN-gamma mAbs. Such treatment impaired the ability of the host to limit parasite multiplication just before and at the time of the peak parasitemia but did not abrogate the development of acquired immunity resulting in control and elimination of acute infection. The requirement of endogenous IFN-gamma around the time of the peak parasitemia was confirmed by quantification of IFN-gamma production in vitro by spleen cells from infected animals in response to malaria antigen. To investigate the role of TNF, resistant C57BL/6 and susceptible A/J mice were treated with rTNF during P. chabaudi AS infection. Treatment with 10(3) or 10(5) U rTNF resulted in increased resistance in A/J hosts (that is, increased survival and a less severe course of infection); there was no difference between control and treated C57BL/6 mice in the course of infection but there was increased mortality among the animals treated with rTNF. Splenic macrophages harvested from C57BL/6 mice during infection were found to produce high levels of TNF from day 3 to day 28 post-infection. In conclusion, both IFN-gamma and TNF appear to contribute to host resistance to blood-stage infection with P. chabaudi AS.
Stevenson
M M
MM
Centre for the Study of Host Resistance, McGill University, Montreal, Quebec, Canada.
Tam
M F
MF
Nowotarski
M
M
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma