Toxo has a ticket to ride

Lethal shock is subverted by crippling a family of G proteins in endothelial cells, according to Korhonen and colleagues on page 411. Bee stings or other allergens can cause anaphylactic shock in severely allergic individuals by triggering mast cell activation and the release of anaphylactic mediators like histamine and platelet activating factor (PAF). At high enough levels, these mediators cause blood pressure to drop precipitously and vessels to leak, eventually leading to shock. Although much is known about causes and consequences of anaphylaxis, the precise pathogenic pathways remain murky. Here, investigators find that shock was sidestepped in mice whose endothelia lacked the G protein go-betweens G q /G 11. Many anaphylactic mediators act through G protein–coupled receptors, which link to downstream signaling molecules via G proteins, turned out to be vital for opening the endothelial barrier and activating endothelial cells during an allergic reaction. Without G q /G 11 , there was no phosphorylation of myosin light chain, which allows endothelial cells to retract from one another. G q /G 11 was also needed for the production of nitric oxide, a known mediator of anaphylactic shock. On the other hand, endothelium-specific ablation of G 12 /G 13 , which activates the Rho/Rho-kinase pathway, had no effect on allergen-induced shock. And the effects of disabling G i remain to be seen. An endothelium-specific antagonist of a downstream player such as G q /G 11 could improve treatment for people at risk of allergen-induced shock. Epinephrine injections can be given only after anaphylaxis has begun, and upstream inhibitors of PAF have been ineffective. A pharmacological G q /G 11 inhibitor has already been developed and awaits testing in preclinical trials. 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 …