Immune responses associated with early survival after peroral infection with Toxoplasma gondii.
After peroral infection with cysts of Toxoplasma gondii, C57BL/6 mice died and A/J mice survived. To better understand the reasons for this difference in survival, host defenses during acute infection were studied: initial portal of entry of T. gondii contributed to susceptibility as more C57BL/6 mice survived after i.p. than peroral infection (p less than 0.001). Susceptible (C57BL/6) mice had more necrosis and inflammation in their brains, livers, and mesenteric lymph nodes than resistant (A/J) mice. Susceptible mice had less IgM antibody to T. gondii (p less than 0.0005) than resistant mice 7 days after infection, but amounts of IgG antibody to T. gondii were similar. Infection reduced percentages of spleen cells with the Lyt-2+ phenotype in susceptible (p less than 0.02) but not resistant mice; infection decreased percentages of spleen cells with the L3T4+ phenotype similarly in both strains of mice. Spleen cells from infected susceptible mice had greater depression in their blastogenic response to Con A (p less than 0.05) and produced significantly more IFN-gamma in culture with (p = 0.009) or without (p less than 0.05) Toxoplasma Ag than spleen cells from infected resistant mice. Infection increased serum levels of IFN-gamma substantially in susceptible but not resistant mice. Lymphocyte IL-2 production was similar in both groups of mice. Peritoneal macrophages from both strains of mice became activated to inhibit or kill T. gondii by 7 days after infection, but Kupffer cells became activated only in susceptible mice. These results indicate that increased resistance to peroral Toxoplasma infection is likely to be mediated by a number of immune responses acting together. They suggest that increased susceptibility may result from inadequately regulated inflammatory responses that increase tissue destruction.
McLeod
R
R
Department of Medicine, Michael Reese Medical Center, Chicago, IL 60616.
Eisenhauer
P
P
Mack
D
D
Brown
C
C
Filice
G
G
Spitalny
G
G
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000032:analysis; D001927:Brain Diseases / Q000523:psychology; D003560:Cysts / Q000523:psychology; D004198:Disease Susceptibility; D005260:Female; D007113:Immunity, Innate; D007371:Interferon-gamma; D007728:Kupffer Cells / Q000469:parasitology; D008109:Liver Diseases, Parasitic / Q000209:etiology; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D013045:Species Specificity; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000145:classification; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology* / Q000401:mortality
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007371:Interferon-gamma