Hookworms are intestinal parasitic nematodes that chronically infect ~500 million people. How hookworms successfully overcome host protective mechanisms is unclear, but it may involve hookworm proteins that digest host tissues, or counteract the host’s immune system, or both. To find such proteins in the zoonotic hookworm Ancylostoma ceylanicum , we used mass spectrometry to identify 565 genes encoding excreted-secreted (ES) proteins from adults, and used RNA-seq to identify genes expressed both in young adults (12 days post-infection) and in intestinal and non-intestinal tissues dissected from mature adults (19 days post-infection), infecting hamster hosts that either had normal immune systems or were immunosuppressed by dexamethasone. In adult A. ceylanicum , we observed 1,670 and 1,196 genes with intestine- and non-intestine-biased expression, respectively. Comparing hookworm gene activity in normal versus immunosuppressed hosts, we observed almost no changes of gene activity in 12-day young adults or non-intestinal 19-day adult tissues. However, in intestinal 19-day adult tissues, we observed 1,951 positively immunoregulated genes, and 137 genes that were negatively immunoregulated. Thus, immunoregulation was observed primarily in mature adult hookworm intestine directly exposed to host blood. Of positively immunoregulated intestinal genes, 50.1% (5.3-fold over background) also had male-biased expression, suggesting that male and female A. ceylanicum have different responses to the host immune system. We observed 153 ES genes showing positive immunoregulation in 19-day adult intestine, which disproportionately encoded CAP, ASPR, astacin, TIMP, TIL, ShK, and SCVP proteins, and that were enriched for ES gene orthologs in the dog hookworm Ancylostoma caninum , the human hookworm Necator americanus , or the related sheep parasite Haemonchus contortus . Such a mixture of rapidly evolving and conserved genes could comprise virulence factors enabling infection, provide new targets for vaccines against hookworm, and aid in developing therapies for immune-mediated diseases.
Schwarz et al. (Tue,) studied this question.