Cell-mediated immunity to Toxoplasma gondii develops primarily by local Th1 host immune responses in the absence of parasite replication.
A single inoculation of mice with the live, attenuated Toxoplasma gondii uracil auxotroph strain cps1-1 induces long-lasting immunity against lethal challenge with hypervirulent strain RH. The mechanism for this robust immunity in the absence of parasite replication has not been addressed. The mechanism of long-lasting immunity, the importance of route of immunization, cellular recruitment to the site of infection, and local and systemic inflammation were evaluated. Our results show that infection with cps1-1 elicits long-lasting CD8+ T cell- mediated immunity. We show that immunization with cps1-1-infected dendritic cells elicits long-lasting immunity. Intraperitoneal infection with cps1-1 induced a rapid influx of GR1+ neutrophils and two stages of GR1+CD68+ inflammatory monocyte infiltration into the site of inoculation. CD19+ B cells and CD3+ T cells steadily increase for 8 days after infection. CD8+ T cells were rapidly recruited to the site of infection and increased faster than CD4+ T cells. Surprisingly, cps1-1 infection induced high systemic levels of bioactive IL-12p70 and a very low level and transient systemic IFN-gamma. Furthermore, we show significant levels of these inflammatory cytokines were locally produced at the site of cps1-1 inoculation. These findings offer new insight into immunological mechanisms and local host responses to a non-replicating type I parasite infection associated with development of long-lasting immunity to Toxoplasma gondii.
Gigley
Jason P
JP
Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Fox
Barbara A
BA
Bzik
David J
DJ
D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000637:transplantation; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D014122:Toxoplasma / Q000254:growth & development* / Q000276:immunology*; D014123:Toxoplasmosis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control
D016052:Protozoan Vaccines; D007371:Interferon-gamma