Fig 1.
Simplified life cycle of Toxoplasma gondii.
Many mammals and birds can serve as intermediate hosts of T. gondii. In these hosts, tachyzoites drive systemic infection. At some point, tachyzoites transform into cyst-forming bradyzoites that persist chronically for the lifetime of the host. When cats consume bradyzoite cysts, a different developmental pathway ensues. Several asexual replication cycles in the intestinal epithelium (merogony) are followed by differentiation into male and female gametes. Fertilization results in an immature oocyst that is shed with the feces into the environment. Meiosis and formation of infectious sporozoites occurs over the course of several days in the environment. Sporulated oocysts are highly infectious to intermediate and final hosts.
Fig 2.
Toxoplasma gondii recognizes its final host, the cat, based on the abundance of the fatty acid linoleic acid.
Most mammals, including mice, metabolize the linoleic acid they take up with their food into arachidonic acid. The enzyme Δ-6-desaturase is the committed step of this pathway. Cats lack this enzyme and thus accumulate linoleic acid to levels higher than other mammals. In the mouse, T. gondii follows an entirely asexual developmental path that leads to bradyzoite cysts in the brain of the mouse. When cats consume these cysts, a sexual program unfolds that leads to oocyst shedding with the feces. Martorelli Di Genova and colleagues [1] blocked Δ-6-desaturase in mice, leading to artificial accumulation of linoleic acid. Remarkably, when these mice are infected with T. gondii, they shed oocysts, identifying linoleic acid as the key to the recognition of the final host. SC26196, inhibitor of Δ-6-desaturase activity.