A vacuole encapsulating a parasite of warm-blooded animals shuttles peptides for cross-presentation in a report from Goldszmid and colleagues on page 399.
Pathogens that get sequestered in host cell vacuoles pose a paradox to immunologists. Although they are kept out of their host cells' cytoplasm, where MHC class I T cell epitopes are normally generated, many still elicit a CD8+ T cell response. Here, Goldszmid et al. use Toxoplasma gondii, a vacuole-trapped bug, to understand how exogenous peptides in dendritic cells move into the cytoplasm in a poorly understood process known as cross-presentation.
Their findings differ from earlier claims that phagasome membranes fuse to the ER to transfer antigens from the vaccuole to class I molecules in the ER. Instead of a phagosome delivery, the authors show that the parasite-containing vacuole fused directly to the ER and presumably allowed antigens to pass between the organelles.
The previous experiments on ER delivery used phagocytosed ovalbumin-coated latex beads as model antigens. This group now moves one step closer to reality by tracking the process using infection with T. gondii expressing a peptide from ovalbumin. The authors hope their model will eventually be verified with unmanipulated T. gondii epitopes.
Proof for vacuole–ER fusion could be provided by blocking the fusion event, but the signals that initiate fusion are completely unknown. Goldszmid speculates that the parasite itself initiates the signal because it benefits from the generation of a CD8+ T cell response, which permits host survival. By being ingested, T. gondii infects more than one animal in its lifetime. Therefore, the parasite is better off sparing the life of its initial, rodent host until a fat cat comes along.