Phagocyte-Derived Reactive Oxygen Species Do Not Influence the Progression of Murine Blood-Stage Malaria Infections

Abstract

Phagocyte-derived reactive oxygen species have been implicated in the clearance of malaria infections. We investigated the progression of five different strains of murine malaria in gp91 phox؊/؊ mice, which lack a functional NADPH oxidase and thus the ability to produce phagocyte-derived reactive oxygen species. We found that the absence of functional NADPH oxidase in the gene knockout mice had no effect on the parasitemia or total parasite burden in mice infected with either resolving (Plasmodium yoelii and Plasmodium chabaudi K562) or fatal (Plasmodium berghei ANKA, Plasmodium berghei K173 and Plasmodium vinckei vinckei) strains of malaria. This lack of effect was apparent in both primary and secondary infections with P. yoelii and P. chabaudi. There was also no difference in the presentation of clinical or pathological signs between the gp91 phox؊/؊ or wild-type strains of mice infected with malaria. Progression of P. berghei ANKA and P. berghei K173 infections was unchanged in glutathione peroxidase-1 gene knockout mice compared to their wild-type counterparts. The rates of parasitemia progression in gp91 phox؊/؊ mice and wild-type mice were not significantly different when they were treated with L-N G -methylarginine, an inhibitor of nitric oxide synthase. These results suggest that phagocyte-derived reactive oxygen species are not crucial for the clearance of malaria parasites, at least in murine models.

A central role for free heme in the pathogenesis of severe malaria: the missing link?

“…Based on the observation that NAD(P)H gp91 phox -deficient mice can develop cerebral malaria, it has been suggested that ROS are probably not involved in its pathogenesis [86]. Our interpretation is somehow different.…”

Macrophage-Mediated but Gamma Interferon-Independent Innate Immune Responses Control the Primary Wave ofPlasmodium yoeliiParasitemia

“…Rather, our data suggest that P. yoelii-infected red blood cells can directly activate macrophages to carry out their effector functions and that these activated macrophages then mediate direct antiparasitic effects. The mechanisms by which macrophages kill or cripple blood-stage parasites are somewhat unclear; despite several studies reporting a role for reactive oxygen intermediates in parasite killing (7,8,9,11), this respiratory burst does not seem to be essential, since gp91 phoxϪ/Ϫ mice lacking the NADPH oxidase system are no more susceptible to P. yoelii, P. chabaudi, or P. berghei infections than wild-type mice are (39).…”

Twofold cost of reproduction: an increase in parental effort leads to higher malarial parasitaemia and to a decrease in resistance to oxidative stress

“…The reactive oxygen species released by leucocytes play a major role in the immune response against Plasmodium parasites and have been associated with efficient parasite clearance [66 -68]. Nevertheless, the exact mechanisms involved are controversial [69,70] and the release of reactive oxygen species in the circulation may on some occasions have more pathological than beneficial effects [29,71].…”