Role of IFN-gamma in lethal and nonlethal malaria in susceptible and resistant murine hosts.
IFN-gamma plays an important role in host defense against microbial disease. Here, we studied the role of IFN-gamma in lethal and nonlethal murine malaria. Administration of recombinant murine IFN-gamma resulted in a dose-dependent protection of SW, BALB/cByJ, and CBA/J mice from the lethal variant of Plasmodium yoelii 17x (PyL) but had little effect on the course of the nonlethal variant of this parasite (PyNL). Administration of recombinant IFN-gamma also resulted in the activation of peritoneal macrophages for increased phagocytosis of malaria-infected erythrocytes and release of H2O2, as measured in vitro. The ability of spleen cells from infected mice to produce endogenous IFN-gamma and release H2O2 during the course of malaria was also studied. In BALB/cByJ mice, which are relatively susceptible to PyL and PyNL, there was an initial burst of IFN-gamma only in response to PyNL whereas in CBA/J mice, which are relatively resistant to these parasites, there was an initial burst of IFN-gamma in response to both PyL and PyNL. The kinetics of H2O2 release corresponded to that of IFN-gamma. In all infections, levels of IFN-gamma declined as parasitemia increased; however, nonlethal infections were characterized by a recovery of both IFN-gamma activity and H2O2 release as parasitemia declined. These data suggest that IFN-gamma may play an important role in modulating the course of malaria infections by activating macrophages for both intracellular and extracellular parasite destruction.
Shear
H L
HL
Department of Medical and Molecular Parasitology, New York University Medical Center 10016.
Srinivasan
R
R
Nolan
T
T
Ng
C
C
D000818:Animals; D004198:Disease Susceptibility; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D008288:Malaria / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D010967:Plasmodium yoelii / Q000276:immunology; D013045:Species Specificity
D007371:Interferon-gamma; D006861:Hydrogen Peroxide