Interleukin-12-dependent mechanisms in the clearance of blood-stage murine malaria parasite Plasmodium berghei XAT, an attenuated variant of P. berghei NK65.
The mechanism of development of host resistance to blood-stage malarial infection was studied by use of an irradiation-induced attenuated variant, Plasmodium berghei XAT, obtained from a lethal strain, P. berghei NK65. The infection enhanced mRNA expression of interleukin (IL)-12 p40 and also of interferon (IFN)-gamma, IL-4, IL-10, and cytokine-inducible nitric oxide synthase (iNOS) in spleen. Treatment of these mice with anti-IL-12 or anti-IFN-gamma led to the progression of parasitemia and fatal outcome. Anti-IL-12 treatment significantly reduced the secretion and mRNA expression of IFN-gamma and greatly diminished the augmentation of iNOS mRNA expression. In addition, recombinant IL-12 administration delayed the onset of parasitemia because of the enhanced IFN-gamma production. These results suggest that blood-stage P. berghei XAT infection induces IL-12 production, which is important for the development of host resistance via IFN-gamma production.
Yoshimoto
T
T
Department of Allergology, Institute of Medical Science, University of Tokyo, Japan. yoshimot@ims.u-tokyo.ac.jp
Yoneto
T
T
Waki
S
S
Nariuchi
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D015870:Gene Expression; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D009500:Neutralization Tests; D010962:Plasmodium berghei / Q000276:immunology* / Q000472:pathogenicity / Q000528:radiation effects; D012333:RNA, Messenger; D013154:Spleen / Q000378:metabolism; D014613:Vaccines, Attenuated / Q000276:immunology
D000911:Antibodies, Monoclonal; D016207:Cytokines; D012333:RNA, Messenger; D014613:Vaccines, Attenuated; D018664:Interleukin-12; D007371:Interferon-gamma