The role of IL-4 in adult acquired and congenital toxoplasmosis.
The course of Toxoplasma gondii infection was studied in IL-4-deficient mice from three genetic backgrounds and their wild-type counterparts following peroral inoculation of tissue cysts. Survival rates were significantly reduced in disease-susceptible C57 BL/6 mice and F1 (C57BL/6 x 129Sv) mice deficient in IL-4 compared with wild-type controls. In contrast, this difference was not observed in T. gondii-resistant BALB/c mice. However, brain tissue cyst burdens in IL-4-deficient mice were either equivalent to (C57BL/6 and BALB/c mice) or significantly less (B6/129 mice) than similarly infected wild-type mice. Thus strain-specific differences in the course of T. gondii were demonstrated in the absence of IL-4. The course of T. gondii infection was also compared between B6/129 IL-4-deficient mice and their wild-type counterparts following peroral challenge with 20 tissue cysts on day 12 of pregnancy. Age-matched non-pregnant IL-4-/- and IL-4+/+ mice were also infected to assess the role of IL-4 on T. gondii infection during pregnancy. Disease phenotypes, as measured by mortality, were reversed if infections were initiated during pregnancy compared with non-pregnant infection. Thus significant mortality occurred immediately post partum in IL-4+/+ mothers, while all IL-4-/- mothers survived. Cyst burdens 28 days p.i. were significantly lower in IL-4-/- mothers than IL-4+/+ mothers and both IL-4-/- and IL-4+/+ non-pregnant mice. Congenital disease transmission as measured by foetal death or vertical disease transmission was independent of the presence or absence of IL-4. These studies demonstrate a role for IL-4 in pregnancy-induced immunosuppression and the associated increased susceptibility to T. gondii infection.
Alexander
J
J
Department of Immunology, University of Strathclyde, Glasgow, UK. j.alexander@strath.ac.uk
Jebbari
H
H
Bluethmann
H
H
Brombacher
F
F
Roberts
C W
CW
D000818:Animals; D004198:Disease Susceptibility; D005260:Female; D018445:Infectious Disease Transmission, Vertical; D015847:Interleukin-4 / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology*; D013045:Species Specificity; D015996:Survival Rate; D014122:Toxoplasma / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology* / Q000635:transmission; D014774:Virulence
D015847:Interleukin-4