Kinetics of nitric oxide production during infection and reinfection of mice with Plasmodium chabaudi.
We have shown previously that at the time of peak primary parasitaemia of P. chabaudi infection in NIH mice, significant levels of nitric oxide are produced, detectable as nitrate in the serum, and that these contribute to the protective immune response to infection. Here, we demonstrate that following reinfection, mice show a markedly diminished ability to produce nitrate. However, if mice are treated with L-NG-monomethyl arginine specifically to block nitric oxide metabolism during the primary infection, and are then reinfected, production of nitrate is restored to levels approaching those attained at peak primary parasitaemia. These experiments, together with others we have reported, indicate that whereas nitric oxide appears to play a significant role in control of the primary parasitaemia of P. chabaudi infection, it performs no such function during subsequent patent parasitaemias. Furthermore, they suggest that factors as yet unknown may regulate nitric oxide activity during malaria infection, such that under normal circumstances its production comes under strict control. This is exemplified by the observation that after the burst of nitric oxide activity that coincides with peak primary parasitaemia, there follows a prolonged period of immunological tolerance during which nitrate levels remain low even at secondary challenge infection. This tolerized state is lifted only several months after initial infection, when the nitric oxide activity at reinfection appears to correlate with the size of the parasite challenge and the presence of a patent parasitaemia. The implications of these findings for protective immunity to malaria, malarial immunosuppression, and immunoregulation in general, are discussed.
Taylor-Robinson
A W
AW
Wellcome Laboratories for Experimental Parasitology, University of Glasgow, UK.
Severn
A
A
Phillips
R S
RS
D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007108:Immune Tolerance; D007700:Kinetics; D008288:Malaria / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000276:immunology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D018512:Parasitemia / Q000276:immunology / Q000378:metabolism; D016788:Plasmodium chabaudi; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase