[Exploration of immune response in a murine model of congenital toxoplasmosis].
We used a model of acquired toxoplasmosis to study the immune response in pregnant BALB/c mice (IL4+/+) and in pregnant transgenic IL4-deficient BALB/c mice (IL4-/-) during acute toxoplasmosis. Female BALB/c mice were infected orally by 20 tissue cysts of the avirulent PRU strain of Toxoplasma gondii on day 11 of pregnancy. After infection, cultured spleen cells from pregnant mice produced more IFN gamma (a type 1 cytokine) and more NO than non pregnant mice, and the type 2 response (IL4 and IL10) was weak. Although this kind of immune response may be required for mice to recover from toxoplasmosis, pregnant mice were more susceptible to infection than non pregnant mice, as illustrated by a larger parasite load in lungs and brain. Pregnant IL4-/- mice showed lower susceptibility to T. gondii infection and a lower materno-fetal transmission rate (24% versus 53% infected fetus) without increased production of type 1 cytokines (IFN gamma and NO). These data indicate that type 2 response plays an important role in increasing mouse susceptibility to T. gondii infection during pregnancy and that IL4 and pregnancy-associated substances increase the transplacental passage of T. gondii. This is the first time that biased towards type 2 immune response induced by pregnancy was shown to increase susceptibility to T. gondii.
Thouvenin
M
M
Institut de parasitologie et de pathologie tropicale, Unité Inserm U. 392, Strasbourg, France.
Candolfi
E
E
Villard
O
O
Kien
T
T
D000818:Animals; D000917:Antibody Formation; D004195:Disease Models, Animal; D005260:Female; D007111:Immunity, Cellular; D007370:Interferon Type I / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009569:Nitric Oxide / Q000378:metabolism; D011247:Pregnancy; D014124:Toxoplasmosis, Animal / Q000151:congenital* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D007370:Interferon Type I; D015847:Interleukin-4; D009569:Nitric Oxide; D007371:Interferon-gamma