The helminth Schistosoma mansoni cannot develop productively in hosts deficient in recombination-activating gene 1 (Rag1−/− hosts); this suggests that an intact host immune system is necessary for parasite growth, but the precise nature of the signals required remains unclear. In PLoS Pathogens, Davies and colleagues find that infection with S. mansoni results in hepatocyte necrosis in wild-type mice but not in Rag1−/− mice. Recapitulating that injury in Rag1−/− mice with hepatotoxic drugs or via challenge with endogenous damage-associated molecular patterns can partially restore parasite development. Such treatment results in the release of inflammatory cytokines, which is reined in by innate tolerance mechanisms after a few weeks. That tolerance is critical for the parasite because if the inflammation is maintained chronically, their growth is completely repressed. Administration of IL-4 is also able to restore parasite growth in Rag1−/− mice, again through the antagonism of inflammatory responses. Therefore, the developmental fate of S. mansoni seems to be intimately entwined with the prevailing host immune response.

PLoS Pathog. (10 October 2013) doi:10.1371/journal.ppat.1003708