Toxoplasma gondii is an intracellular parasite that infects warm blooded animals, including humans. In these hosts, Toxoplasma establishes a chronic infection in the brain, which the parasite accomplishes in part by injecting effector proteins, which manipulate many cellular processes, into cells it invades. Two recent reports suggested that Toxoplasma may also inject effector proteins into cells it does not invade. To look for these “uninfected-injected” cells, researchers utilized three different reporter systems that are tied to injection of effector proteins and not to invasion. They showed that Toxoplasma injects proteins into cells it does not invade and enough protein is injected to manipulate the uninfected cells in a manner consistent with what occurs in infected cells.
Using one of the reporter systems in mice showed that uninfected-injected cells can include systemic immune cells and neurons in the brain. Remarkably, in the brain, the uninfected-injected cells out-number the infected cells by many fold. Together, these results strongly suggest that Toxoplasma manipulates far more cells than previously realized and, given their abundance, these uninfected-injected cells may play a central role in how Toxoplasma engages the host’s immune response.
Toxoplasma Co-opts Host Cells It Does Not Invade. (2012) PLoS Pathog 8(7): e1002825. doi:10.1371/journal.ppat.1002825
Like many intracellular microbes, the protozoan parasite Toxoplasma gondii injects effector proteins into cells it invades. One group of these effector proteins is injected from specialized organelles called the rhoptries, which have previously been described to discharge their contents only during successful invasion of a host cell. In this report, using several reporter systems, we show that in vitro the parasite injects rhoptry proteins into cells it does not productively invade and that the rhoptry effector proteins can manipulate the uninfected cell in a similar manner to infected cells. In addition, as one of the reporter systems uses a rhoptry:Cre recombinase fusion protein, we show that in Cre-reporter mice infected with an encysting Toxoplasma-Cre strain, uninfected-injected cells, which could be derived from aborted invasion or cell-intrinsic killing after invasion, are actually more common than infected-injected cells, especially in the mouse brain, where Toxoplasma encysts and persists. This phenomenon has important implications for how Toxoplasma globally affects its host and opens a new avenue for how other intracellular microbes may similarly manipulate the host environment at large.