SUMMARY The immunopathology caused by schistosome helminths varies greatly in humans and among mouse strains. A severe form of parasite egg-induced hepatic granulomatous inflammation, seen in CBA mice, is driven by Th17 cells stimulated by IL-1β and IL-23 produced by dendritic cells that express CD209a (SIGNR5), a C-type lectin receptor (CLR) related to human DC-SIGN. Here, we show that CD209a-deficient CBA mice display decreased Th17 responses and are protected from severe immunopathology. In vitro, CD209a augments the egg-induced IL-1β and IL-23 production initiated by the related CLRs Dectin-2 and Mincle. While Dectin-2 and Mincle trigger an FcRγ-dependent signaling cascade that involves the tyrosine kinase Syk and the trimolecular Card9-Bcl10-Malt1 complex, CD209a promotes the sustained activation of Raf-1. Our findings demonstrate that CD209a drives severe Th17 cell-mediated immunopathology in a helminthic disease based on synergy between DC-SIGN- and Dectin-2-related CLRs.

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The complexity of trade networks is a major challenge to controlling wildlife trafficking and illegal, unreported, and unregulated (IUU) fishing. These networks may not be modern inventions, but have developed over centuries, from integrated global markets that preceded modern regulatory policies. To understand these linkages, we curated 150 years of tortoiseshell transactions and derived biologically informed harvest models to estimate the trade in critically endangered hawksbill sea turtles (Eretmochelys imbricata). We find that trade networks concentrated in Southeast Asia harvested 9 million turtles, over six times previous estimates. These networks spread from within the Pacific, to the Indian and Atlantic basins, and became markedly more complex after 1950. Our results further indicate that the magnitude and extent of the coastally restricted hawksbill exploitation parallel current patterns of IUU fishing. Policies to combat these interlinked illegal practices should assimilate the important role of small-scale, coastal fisheries in these increasingly complex global networks.

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