Immune response in a murine model of congenital toxoplasmosis: increased susceptibility of pregnant mice and transplacental passage of Toxoplasma gondii are type 2-dependent.
We used a model of acquired toxoplasmosis to study the immune response in pregnant BALB/c mice (IL-4+/+) and in pregnant transgenic IL-4-deficient BALB/c mice (IL-4-/-) 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. Splenocyte cultures were used to explore proliferative responses and cytokine production in vitro. Parasite loads were determined in the lungs on day 7 post-infection and in the brain on day 30 post-infection. After infection, cultured spleen cells from pregnant mice produced more IFN-gamma (a Type I cytokine) and more NO than non pregnant mice, and the Type 2 response (IL-4 and IL-10) 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 IL-4-/- mice showed lower susceptibility to T. gondii infection and a lower materno-fetal transmission rate (24% vs. 53% infected fetuses) without increased production of Type I 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 IL-4 and pregnancy-associated substances increase the transplacental passage of T. gondii.
Thouvenin
M
M
Institut de Parasitologie, Strasbourg, France.
Candolfi
E
E
Villard
O
O
Klein
J P
JP
Kien
T
T
D000818:Animals; D001921:Brain / Q000469:parasitology; D004198:Disease Susceptibility; D005260:Female; D015847:Interleukin-4 / Q000172:deficiency / Q000502:physiology*; D008168:Lung / Q000469:parasitology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology; D010920:Placenta / Q000276:immunology / Q000469:parasitology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000523:psychology; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014122:Toxoplasma / Q000302:isolation & purification / Q000502:physiology; D014124:Toxoplasmosis, Animal / Q000151:congenital / Q000276:immunology* / Q000635:transmission; D016781:Toxoplasmosis, Cerebral / Q000276:immunology
D008222:Lymphokines; D015847:Interleukin-4; D009569:Nitric Oxide