The role of IL-18 in blood-stage immunity against murine malaria Plasmodium yoelii 265 and Plasmodium berghei ANKA.
A possible protective role of IL-18 in host defense against blood-stage murine malarial infection was studied in BALB/c mice using a nonlethal strain, Plasmodium yoelii 265, and a lethal strain, Plasmodium berghei ANKA. Infection induced an increase in mRNA expression of IL-18, IL-12p40, IFN-gamma, and TNF-alpha in the case of P. yoelii 265 and an increase of IL-18, IL-12p40, and IFN-gamma in the case of P. berghei ANKA. The timing of mRNA expression of IL-18 in both cases was consistent with a role in the induction of IFN-gamma protein expression. Histological examination of spleen and liver tissues from infected controls treated with PBS showed poor cellular inflammatory reaction, massive necrosis, a large number of infected parasitized RBCs, and severe deposition of hemozoin pigment. In contrast, IL-18-treated infected mice showed massive infiltration of inflammatory cells consisting of mononuclear cells and Kupffer cells, decreased necrosis, and decreased deposition of the pigment hemozoin. Treatment with rIL-18 increased serum IFN-gamma levels in mice infected with both parasites, delayed onset of parasitemia, conferred a protective effect, and thus increased survival rate of infected mice. Administration of neutralizing anti-IL-18 Ab exacerbated infection, impaired host resistance and shortened the mean survival of mice infected with P. berghei ANKA. Furthermore, IL-18 knockout mice were more susceptible to P. berghei ANKA than were wild-type C57BL/6 mice. These data suggest that IL-18 plays a protective role in host defense by enhancing IFN-gamma production during blood-stage infection by murine malaria.
Singh
Ram Pyare
RP
Malaria Research Group, International Center for Genetic Engineering and Biotechnology, New Delhi, India.
Kashiwamura
Shin-ichiro
S
Rao
Prakash
P
Okamura
Haruki
H
Mukherjee
Askok
A
Chauhan
Virander Singh
VS
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D018450:Disease Progression; D004198:Disease Susceptibility; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D007371:Interferon-gamma / Q000097:blood; D020382:Interleukin-18 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D008099:Liver / Q000276:immunology / Q000473:pathology; D008288:Malaria / Q000097:blood / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010962:Plasmodium berghei / Q000254:growth & development; D010967:Plasmodium yoelii / Q000254:growth & development; D012333:RNA, Messenger / Q000096:biosynthesis; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D015533:Transcriptional Activation
D016207:Cytokines; D020382:Interleukin-18; D012333:RNA, Messenger; D007371:Interferon-gamma