Ecologia celular de populações de células inflamatórias do granuloma na esquistossomose mansônica

Abstract

Schistosomiasis, a neglected parasitic infection, has affected humans for centuries and remains a serious public health problem, with high rates of morbidity and mortality. Currently, there are around 240 million people infected worldwide and 700 million at risk of infection in 78 countries. Schistosomiasis is considered a multifactorial disease with environmental, behavioral, parasitic and host-associated aspects. The main histopathological feature of the disease is the formation of granulomas around the parasite eggs in target organs of vertebrate hosts. Granulomas have been described as dynamic, multifaceted and self-organizing systems with both host and parasite components. However, the functioning of granulomas, in different target organs, and how to restrain their development is still poorly understood. In the present work, we studied granulomas from the point of view of cellular ecology. Classically, ecology is an interdisciplinary, modern, and active science that studies the behavior and interactions of organisms with each other and with the environment. However, ecological perspectives are not limited to just a spatial scale and can also be applied to cells and molecules. In the present work, we studied granulomas from the point of view of cellular ecology. Here, we propose that the hepatic granuloma caused by the parasite S. mansoni acts as an evolving ecosystem. In line with ecological concepts, we examine the granuloma not only as a site where a community of cells is established, but also as a site where the functional activities of these combined populations occur in an orchestrated way in response to microenvironmental gradients, such as cytokines and egg antigens. We also explored the possible roles that eosinophils can play in granulomas. These cells are one of the most abundant populations in granuloma, whose functional roles remain unclear and even controversial. Furthermore, we investigated aspects of the composition and structure of the cellular community of intestinal and hepatic granulomas and their spatial-temporal development during experimental infection with S. mansoni. With the application of the Whole Slide Imaging (WSI) technique and ecological analyses, we show for the first time the spacetime dynamics of the cellular communities of intestinal and hepatic granulomas. We found that the cell populations vary in quantity according to the organ (liver or intestine) and the evolutionary stage of the granuloma. We also investigated the similarity and cellular diversity in the granulomas. Granulomas from the same organ at different evolutionary stages are more similar than granulomas from different organs at the same evolutionary stage. Intestinal granulomas are more diverse than hepatic granulomas. We also identified cellular interactions, mainly between eosinophils and plasma cells with potential functional roles. Our results broaden the understanding of the spatiotemporal dynamics of cell populations in granulomas. A better understanding of the schistosomal granuloma as an ecological system may be the key to unveil the complexity of this inflammatory response and guide future treatment of the disease.