Unresponsiveness to surface antigen 1 modifies cytokine profiles in acute Toxoplasma gondii infection.
Resistance to Toxoplasma gondii involves the development of a highly polarized Th1-type cytokine expression. SAG1 transgenic mice are highly susceptible to T. gondii infection due to their non-reactivity to SAG1 of the protozoan parasite. Here we describe cytokine profiles during the acute phase of T. gondii infection, which are associated with the susceptibility of SAG1 transgenic mice. SAG1 transgenic mice showed a 4.5-fold increase in susceptibility upon inoculation with a sublethal dose of the Beverley strain of T. gondii compared to their wild-type counterparts (mortality: 81 vs. 18%, respectively). When analysis of the most important cytokines involved in the mediation of resistance to infection was carried out, SAG1 transgenic mice exhibited low production levels of IL-12, IFN-gamma and TNF-alpha in sera during the acute phase of T. gondii infection. Antibody and T cells specific for SAG1 were not mounted upon SAG1 stimulation in SAG1 transgenic mice. Moreover, in vitro studies indicated that in SAG1 transgenic mice IFN-gamma and IL-12 production was lower than in their wild-type counterparts, although levels of TNF-alpha increased in SAG1 transgenic mice on day 9 after infection. Low IgG2a levels were detected in SAG1 transgenic mouse sera. Unresponsiveness to SAG1 of T. gondii renders SAG1 transgenic mice unable to develop a strong Th1-based protection against T. gondii infection. These results provide evidence that SAG1 is a pivotal antigen involved in the induction of immune responses towards the development of Th1-protective immunity during T. gondii infection.
Seng
S
S
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan.
Makala
L H C
LH
Maki
Y
Y
Choi
Y
Y
Yokoyama
M
M
Suzuki
N
N
Toyoda
Y
Y
Nagasawa
H
H
D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000097:blood / Q000276:immunology*
D000953:Antigens, Protozoan; D016207:Cytokines; D015800:Protozoan Proteins; C047168:SAG1 antigen, Toxoplasma