title: Toxoplasma gondii induction of interleukin-12 is associated with acute virulence in mice and depends on the host genotype.
abstract: The intracellular parasite Toxoplasma gondii can influence host resistance by modulating immune functions in various cell types. The stimulation of interleukin (IL)-12 production in macrophages, dendritic cells and neutrophils by T. gondii has been implicated to be important for skewing anti-parasite immunity early after infection as well as in mediating the pathologic effects induced by the parasite. The present study demonstrates secretion of IL-12 p40 and the bioactive p70 heterodimer by inflammatory macrophages following exposure to live Toxoplasma or tachyzoite lysate. Parasite induction of IL-12 occurred in a dose-dependent manner. Predigestion of T. gondii lysate with proteinase K abrogated its IL-12 inducing activity, thus indicating that a parasite protein(s) triggers this response. Macrophages from various mouse inbred strains showed a differential responsiveness: cells from T. gondii-susceptible mice released more IL-12 upon toxoplasmic challenge than those from resistant mice, although the infection rate and intracellular parasite growth were similar. In triggering macrophage production of IL-12, tachyzoites proved superior to bradyzoites prepared from the same T. gondii isolate. Furthermore, parasites of a mouse-virulent isolate became less efficient inducers of IL-12 following attenuation. The parallel loss in macrophage stimulation in vitro and acute virulence in vivo suggests a linkage of both parasite capacities. Together with the correlation on host side between the genotype-dependent mouse susceptibility to infection and cellular responsiveness to the parasite trigger, these findings indicate that an overproduction of parasite-induced IL-12 might represent a basic mechanism of T. gondii pathogenicity.
authors.affiliation: Institute for Medical Microbiology and Virology, Heinrich-Heine-University, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Schade
authors.forename: H G
authors.initials: HG
authors.lastname: Fischer
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D004306:Dose-Response Relationship, Immunologic; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005838:Genotype; D018664:Interleukin-12 / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D014122:Toxoplasma / Q000276:immunology / Q000472:pathogenicity*; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology*; D014774:Virulence
chemical_list: D018664:Interleukin-12