Schistosoma mansoni eggs modulate the timing of granuloma formation to facilitate parasite maturation and release

Schistosome eggs provoke formation of granulomas around them. For the host, the granulomatous response can be both protective and pathological. Granulomas are also postulated to facilitate parasite egg extrusion through the gut lumen, a necessary step for transmission. Using zebrafish larvae, we find that mature Schistosoma mansoni eggs recruit macrophages, which form granulomas within days. Inert egg-sized beads also rapidly induce granulomas through a foreign body response. Strikingly, immature S. mansoni eggs do not recruit macrophages. We distinguish mature and immature eggs via size analysis and find that only mature S. mansoni eggs are shed into the feces of infected mice. Importantly, analysis of egg sizes from previously reported data shows that humans also shed mature eggs only. Our findings support the model that the immunologically inert eggshell inhibits granuloma formation long enough for the parasite to mature. Then parasite antigens secreted through the eggshell trigger granulomas, facilitating egg extrusion