IL-4 is protective against development of toxoplasmic encephalitis.
IFN-gamma is critical for prevention of development of toxoplasmic encephalitis (TE). Since IL-4 down-regulates production of IFN-gamma, we examined its role in the pathogenesis of TE in IL-4-targeted mutant (IL-4-/-) mice. IL-4-/- mice all died from 6 to 20 wk after peroral infection with cysts of the ME49 strain of Toxoplasma gondii; control mice survived. At 4 and 8 wk after infection, significantly greater numbers of T. gondii cysts and foci of acute inflammation, and greater amounts of tachyzoite-specific mRNA (by reverse-transcriptase PCR) were in brains of IL-4-/- mice than controls. Toxoplasma IgG2b and IgG3 Ab levels were slightly but significantly higher in sera of IL-4-/- than control mice, whereas IgM and IgG2a levels did not differ between these mice. Toxoplasma IgG1 and IgE Abs were not detected in sera of either strain. Amounts of IFN-gamma, TNF-alpha, IL-6, and IL-10 mRNA detected by reverse-transcriptase PCR did not differ between brains of infected IL-4-/- and controls, although brains of the former mice had greater numbers of inflammatory mononuclear cell infiltrates. IL-4 mRNA was detected only in infected control mice. Spleen cells of control mice at 8 wk after infection produced significantly greater amounts of IFN-gamma following stimulation in vitro with soluble T. gondii Ags than did those from IL-4-/- mice. These results indicate that IL-4 is protective against development of TE by preventing formation of T. gondii cysts and proliferation of tachyzoites in the brain. The impaired ability of IL-4-/- mice in the late stage of T. gondii infection to produce IFN-gamma most likely contributes to their susceptibility for development of severe TE.
Suzuki
Y
Y
Department of Immunology and Infectious Diseases, Research Institute, Palo Alto Medical Foundation, CA 94301.
Yang
Q
Q
Yang
S
S
Nguyen
N
N
Lim
S
S
Liesenfeld
O
O
Kojima
T
T
Remington
J S
JS
D000818:Animals; D004660:Encephalitis / Q000382:microbiology / Q000517:prevention & control*; D015847:Interleukin-4 / Q000172:deficiency / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014122:Toxoplasma / Q000302:isolation & purification; D014124:Toxoplasmosis, Animal / Q000517:prevention & control*
D015847:Interleukin-4