Histological assessment of granulomas in natural and experimental Schistosoma mansoni infections using whole slide imaging

Abstract

The pathology of schistosomiasis mansoni, a neglected tropical disease of great clinical and socioeconomic importance, results from the parasite eggs that become trapped in host tissues, particularly in the liver and intestines. Continuous antigenic stimulation from these eggs leads to recruitment of inflammatory cells to the sites of infection with formation of periovular granulomas. These complex structures have variable size and composition and are the most striking histopathological feature of schistosomiasis mansoni. However, evaluation of granulomas by conventional microscopy methods is time-consuming and limited, especially in large-scale studies. Here, we used high resolution Whole Slide Imaging (WSI), which allows fast scanning of entire histological slides, and multiple morphometric evaluations, to assess the granulomatous response elicited in target organs (liver, small and large intestines) of two models of schistosomiasis mansoni. One of the advantages of WSI, also termed virtual microscopy, is that it generates images that simultaneously offer high resolution and a wide field of observation. By using a model of natural (Nectomys squamipes, a wild reservoir captured from endemic areas in Brazil) and experimental (Swiss mouse) infection with Schistosoma mansoni, we provided the first detailed WSI characterization of granulomas and other pathological aspects. WSI and quantitative analyses enabled a fast and reliable assessment of the number, evolutional types, frequency and areas of granulomas and inflammatory infiltrates and revealed that target organs are differentially impacted by inflammatory responses in the natural and experimental infections. Remarkably, high-resolution analysis of individual eosinophils, key cells elicited by this helminthic infection, showed a great difference in eosinophil numbers between the two infections. Moreover, features such as the intestinal egg path and confluent granulomas were uncovered. Thus, WSI may be a suitable tool for detailed and precise histological analysis of granulomas and other pathological aspects for clinical and research studies of schistosomiasis.

Epigenetic and parasitological parameters are modulated in EBi3-/- mice infected with Schistosoma mansoni

“…Experimental infections in C57BL/6 mice (Mus musculus) generate immunological responses with greater intensity of interleukin IL10 and lower intensity of interleukins IL4 and IL13 when compared with infections in Balb/c mice [4]. Granulomas from rodent infections from natural reservoirs are less aggressive in the liver and more aggressive in the intestine; the composition of the granuloma in these animals is characterized by the presence of extracellular matrix and fewer inflammatory cells [5]. In contrast, Swiss strains infected with S. mansoni exhibit granulomas with extensive inflammatory infiltrates, often involving several eggs and the presence of necrosis [5].…”

“…Granulomas from rodent infections from natural reservoirs are less aggressive in the liver and more aggressive in the intestine; the composition of the granuloma in these animals is characterized by the presence of extracellular matrix and fewer inflammatory cells [5]. In contrast, Swiss strains infected with S. mansoni exhibit granulomas with extensive inflammatory infiltrates, often involving several eggs and the presence of necrosis [5].…”

The ethanolic extract of date palm pollen significantly inhibited granuloma induced by Schistosoma mansoni soluble egg antigen in vitro

“…Continuous antigenic stimulation from these egg secretions leads to recruitment of inflammatory cells to the sites of infection with formation of periovular granulomas [15]. Granulomas protect host tissues by isolating toxins secreted by the egg [16].…”

“…The granulomatous response is also responsible for the pathogenesis of the schistosomiasis, causing severe inflammation, collagen deposition, fibrosis, and portal hypertension [17]. In the liver, granulomas may trigger severe fibrosis, which disrupts blood flow through this organ and causes portal hypertension and may be leading to potentially fatal esophageal bleeding [15].…”

Whole slide imaging is a high-throughput method to assessCandidabiofilm formation

“…In order to obtain more insights into the cohesion of domains inside a biofilm and to investigate whole biofilm architecture normally growing or following exposure to antifungals, we address here the use of a technique new to the field of biofilm research: whole slide imaging (WSI). This approach allows high-resolution, digital visualization of regular glass slides in their entirety with the use of a digital slide scanner thus generating "digital slides" that offer detailed morphological information and possibility for quantification of multiple morphometric parameters (Webster and Dunstan, 2014;Amaral et al, 2017;Melo et al, 2019). Other WSI benefits are digital storage, easy share ability, the possibility to make annotations on the slide, automated data extraction, remote accessibility and educational purposes (Saco et al, 2016).…”