Plasmodium chabaudi chabaudi: differential susceptibility of gene-targeted mice deficient in IL-10 to an erythrocytic-stage infection.
Female and male mice deficient in IL-10 production by targeted disruption of the IL-10 gene were infected with Plasmodium chabaudi chabaudi (AS) blood-stage parasites. Both male and female mutant mice exhibited more severe signs of disease than did +/+ or heterozygous control mice. Female defective mice also displayed an increased mortality; 56% of mice died within 20 days of infection. Mortality did not appear to be due to a fulminating parasitemia as death occurred at different levels of parasitemia in the individual mice. The acute infection was accompanied by an enhanced Th1 IFN-gamma response. This response was retained in the chronic phase of infection of both male and female mutant mice, whereas in controls the responding CD4+ T cells were predominantly Th2 cells secreting IL-4. The data suggest that IL-10 regulates the inflammatory response to the parasite and that in its absence the combined effects of malaria toxins and the sustained or enhanced IFN-gamma response lead to increased pathology. In the case of female mice absence of IL-10 is sufficient to induce a lethal endotoxin-like reaction.
Linke
A
A
Department of Biology, Imperial College of Science, Technology and Medicine, London, United Kingdom.
Kühn
R
R
Müller
W
W
Honarvar
N
N
Li
C
C
Langhorne
J
J
D000740:Anemia / Q000209:etiology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004198:Disease Susceptibility; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D018390:Gene Targeting; D006579:Heterozygote; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis; D008288:Malaria / Q000150:complications / Q000276:immunology* / Q000469:parasitology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia; D016788:Plasmodium chabaudi / Q000254:growth & development / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma