Figure 1.
Integrating phagocyte function with T. gondii infection.
(A) After crossing the epithelium of the small intestine, tachyzoites invade DC and stimulate IL-12 production through the activity of GRA5. Uptake of extracellular parasite debris containing profilin also stimulates IL-12 production. Some parasite strains trigger activation of STAT3 and STAT6 through secretory kinase ROP16, simultaneously down-regulating IL-12 induction. (B) Infected DC migrate to the draining lymph node and beyond, thereby disseminating infection. Infected as well as antigen-bearing DC also initiate immunity in the lymph node. (C) Inflammatory macrophages are recruited from the bone marrow in dependence upon CCR2. Following IFN-γ-mediated induction of IRGM-family effector molecules, intracellular parasites are destroyed by disruption of the parasitophorous vacuole. Some parasite strains release an effector kinase called ROP18 that phosphorylates and inactivates host IRGM molecules. (D) CXCR2-dependent neutrophils are also part of the innate response to Toxoplasma, although their functional importance is debated. In vitro studies have shown that neutrophils release several proinflammatory cytokines important for DC activation and resistance to the parasite. Neutrophils also produce extracellular traps that can ensnare parasites possibly interfering with invasion.