Schistosoma mansoni eggs modulate the timing of granuloma formation to promote transmission

Abstract

Schistosome eggs provoke the formation of granulomas, organized immune aggregates, around them. For the host, the granulomatous response can be both protective and pathological. Granulomas are also postulated to facilitate egg extrusion through the gut lumen, a necessary step for parasite transmission. We used zebrafish larvae to visualize the granulomatous response to Schistosoma mansoni eggs and inert egg-sized beads. Mature eggs rapidly recruit macrophages, which form granulomas within days. Egg-sized inert beads also induce granulomas rapidly, through a foreign body response. Strikingly, immature eggs evade macrophage recruitment altogether, revealing that the eggshell is immunological inert. These findings suggest that the parasite modulates the timing of granuloma formation to its advantage, inhibiting foreign body granuloma formation until it reaches the optimal maturation and location for extrusion. At this point, the parasite secretes specific antigens through the eggshell to trigger granulomas that might facilitate egg extrusion.