Plasmodium, the parasite responsible for malaria, must differentiate once in its life cycle to the sexual stage form, called the gametocyte, to ensure transmission to other hosts. Two new studies show that malaria-infected red blood cells communicate with each other by vesicles, which induces gametocyte production and host immunomodulation (Cell http://dx.doi.org/10.1016/j.cell.2013.04.029; Cell Host Microbe 13, 521–534, 2013).

The two groups provided insights into how blood-stage Plasmodium falciparum communicates in the host. Neta Regev-Rudzki et al. showed that the release of exosome-like vesicles from infected red blood cells before parasite egress enables transfer of genes between parasites. This not only allows parasites to exchange drug resistance genes to promote their survival but also signaling that allows the parasites to differentiate into their sexual forms. Pierre-Yves Mantel et al. found that a larger type of vesicle, microvesicles, caused an increase in gametocyte numbers and also activated innate immune cells to release proinflammatory cytokines, which might contribute to disease. These vesicles contained red blood cell–derived proteins and parasite antigens, but it is unknown what other cargo may be inside and what proteins are responsible for triggering differentiation into the sexual stage.

The studies also show that P. falciparum–infected red blood cells can internalize exosomes and microvesicles and that this uptake increases in conditions of stress and when the blood concentration of vesicles increases. This suggests that parasite crosstalk may lead to optimized gametocyte production and transmission to mosquitoes. This vesicle-mediated transport could be targeted to block parasite transmission and reduce disease progression.