A protective role for IL-6 during early infection with Toxoplasma gondii.
IL-6 deficient mice were found to be significantly more susceptible to peroral infection with Toxoplasma gondii than their wild-type counterparts as measured by survival, brain cyst burdens and brain pathology at 28 days post infection. The physical manifestations of disease, such as weight loss, were not observed in IL-6 deficient animals until at least seven days later than such changes occurred in wildtype mice. During this early stage of infection IL-6+/+ but not IL-6-/- mice mounted a peripheral blood neutrophilia. Furthermore, between 6-8 days post-infection there was a significant increase in plasma IFN-gamma levels in wild-type but not IL-6 deficient mice. Not until days 18-23 post-infection, concurrent with the majority of deaths in IL-6-/- mice, were plasma IFN-gamma levels substantially and significantly raised in IL-6-/- mice. At this time not only were these plasma IFN-gamma levels 20-fold higher than background but eight-fold greater than peak (6-8 days post-infection) IFN-gamma levels in IL-6+/+ mice. IFN-gamma dependent parasite specific IgG2a levels were also significantly higher in IL-6-/- mice over this period and thereafter. Overall the evidence suggests that in the absence of IL-6 mice are unable to initiate a rapid proinflammatory response against T. gondii, which allows increased parasite growth. Increased mortality in IL-6-/- mice may be directly due to this increased parasite burden and the excessive inflammatory response this induces three weeks post-infection.
Jebbari
H
H
Department of Immunology, University of Strathclyde, Todd Centre, Glasgow, UK.
Roberts
C W
CW
Ferguson
D J
DJ
Bluethmann
H
H
Alexander
J
J
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D001921:Brain / Q000469:parasitology / Q000473:pathology; D003560:Cysts / Q000469:parasitology; D005260:Female; D017353:Gene Deletion; D007371:Interferon-gamma / Q000097:blood; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology*; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000166:cytology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014122:Toxoplasma / Q000276:immunology*; D014124:Toxoplasmosis, Animal / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000469:parasitology; D015431:Weight Loss
D000913:Antibodies, Protozoan; D015850:Interleukin-6; D007371:Interferon-gamma