Distribuição espacial de eosinófilos no microambiente da inflamação granulomatosa intestinal durante a infecção experimental por Schistosoma mansoni

Abstract

Eosinophils are multifunctional cells with an important role in parasitic diseases, such as schistosomiasis mansoni—a neglected tropical disease caused by the parasite Schistosoma mansoni. One of the main pathological characteristics of the disease is the formation of granulomas in target organs, such as the liver and intestines. Granulomas are dynamic structures formed by a cluster of immune cells arranged around the parasite's egg, associated with the translocation of eggs through the intestinal wall and their entrapment in the liver. In liver infection, eosinophils robustly colonize schistosoma granulomas and occupy an ecological niche at the periphery of this microenvironment. However, little is known about the spatial distribution of eosinophils in intestinal granulomas. In this study, we mapped granulomatous inflammation and the spatial distribution of eosinophils in granulomas throughout the intestinal tract of mice with acute S. mansoni infection. Using a set of methodologies including histopathological techniques, immunofluorescence, flow cytometry, Whole Slide Imaging, and quantitative image analysis, the results demonstrated that the small intestine (SI) is more affected by granulomatous inflammation compared to the large intestine (LI). With granulomas preferentially present in the submucosa, a predominance of a more immature granuloma stage (pre-granulomatous exudative /PE) was shown throughout the intestinal tract. This reveals a characteristic dynamic of intestinal granulomas, probably favoring the translocation of parasite eggs. Eosinophils intensely colonize PE granulomas, but in mature granulomas, they are spatially organized and predominantly occupy a medial-peripheral niche. Within this ecological niche, there is a presence of both mature and immature eosinophil populations and compartmentalization of the cationic protein MBP-1, one of the main products of eosinophils. During infection, different eosinophil subpopulations are found in the intestine, indicating modulation of the inflammatory response. Our results, demonstrating an ecological niche of eosinophils, unrelated to parasite eggs, do not favor a direct role of these cells against the parasite. The findings advance the understanding of the functionalities of granulomas and eosinophils during intestinal schistosomiasis mansoni.