A major ecological niche of eosinophils in evolving <i>Schistosoma</i> granulomas challenges the eosinophil view as “helminth killer” cells

Eosinophil-rich granulomas, formed around tissue-trapped parasite eggs, are hallmarks of schistosomiasis mansoni, a prevalent neglected tropical disease. How eosinophils populate and affect the complex <i>Schistosoma</i> granulomas remains unclear. Here, we mapped eosinophils across evolutional hepatic granulomas in a mouse model and in a primary wild reservoir for human schistosomiasis in Brazil (water rat <i>Nectomys squamipes</i>). With in-depth quantitative image analysis and three-dimensional histological reconstructions of entire granulomas, we find that eosinophils are spatially organized and occupy a major, peripheral niche conserved across space and time in all granuloma stages and both experimental and natural infections. Within this niche, immature and mature eosinophils coinhabit, compartmentalize their major basic protein-1 content, robustly interact with other immune cells, and secrete through piecemeal degranulation. This unveiled niche, unrelated to parasite eggs, challenges the concept of eosinophil as a "helminth killer" cell and invigorates its view as an immunoregulatory cell of the tissue microenvironment in <i>Schistosoma</i> granulomas.