将血吸虫肉芽肿的观点转变为生态立场。

Changing our view of the Schistosoma granuloma to an ecological standpoint.

机构信息

Laboratory of Cellular Biology, Department of Biology, Federal University of Juiz de Fora, Rua José Lourenço Kelmer, São Pedro, Juiz de Fora, MG, 36036-900, Brazil.

Graduate Program in Biodiversity, Federal University of Juiz de Fora, Rua José Lourenço Kelmer, São Pedro, Juiz de Fora, MG, 36036-900, Brazil.

出版信息

Biol Rev Camb Philos Soc. 2021 Aug;96(4):1404-1420. doi: 10.1111/brv.12708. Epub 2021 Mar 22.

Abstract

Schistosomiasis, a neglected parasitic tropical disease that has plagued humans for centuries, remains a major public health burden. A primary challenge to understanding schistosomiasis is deciphering the most remarkable pathological feature of this disease, the granuloma - a highly dynamic and self-organized structure formed by both host and parasite components. Granulomas are considered a remarkable example of how parasites evolved with their hosts to establish complex and intimate associations. However, much remains unclear regarding life within the granuloma, and strategies to restrain its development are still lacking. Here we explore current information on the hepatic Schistosoma mansoni granuloma in the light of Ecology and propose that this intricate structure acts as a real ecosystem. The schistosomal granuloma is formed by cells (biotic component), protein scaffolds, fibres, and chemical compounds (abiotic components) with inputs/outputs of energy and matter, as complex as in classical ecosystems. We review the distinct cell populations ('species') within the granuloma and examine how they integrate with each other and interact with their microenvironment to form a multifaceted cell community in different space-time frames. The colonization of the hepatic tissue to form granulomas is explained from the point of view of an ecological succession whereby a community is able to modify its physical environment, creating conditions and resources for ecosystem construction. Remarkably, the granuloma represents a dynamic evolutionary system that undergoes progressive changes in the 'species' that compose its community over time. In line with ecological concepts, we examine the granuloma not only as a place where a community of cells is settled (spatial niche or habitat) but also as a site in which the functional activities of these combined populations occur in an orchestrated way in response to microenvironmental gradients such as cytokines and egg antigens. Finally, we assert how the levels of organization of cellular components in a granuloma as conventionally defined by Cell Biology can fit perfectly into a hierarchical structure of biological systems as defined by Ecology. By rethinking the granuloma as an integrating and evolving ecosystem, we draw attention to the inner workings of this structure that are central to the understanding of schistosomiasis and could guide its future treatment.

摘要

血吸虫病是一种被忽视的热带寄生虫病,困扰人类已有数百年之久,仍是主要的公共卫生负担。理解血吸虫病的一个主要挑战是破解这种疾病最显著的病理特征,即肉芽肿——一种由宿主和寄生虫成分组成的高度动态和自组织结构。肉芽肿被认为是寄生虫与宿主进化建立复杂而密切联系的一个显著例子。然而,对于肉芽肿内的生命以及限制其发展的策略,仍有许多不清楚的地方。在这里,我们根据生态学探讨曼氏血吸虫肝脏肉芽肿的现有信息,并提出这个复杂结构充当真正的生态系统。血吸虫肉芽肿由细胞(生物成分)、蛋白质支架、纤维和化学化合物(非生物成分)组成,具有能量和物质的输入/输出,与经典生态系统一样复杂。我们回顾了肉芽肿内不同的细胞群体(“物种”),并研究了它们如何相互整合以及与微环境相互作用,在不同的时空框架下形成一个多方面的细胞群落。从生态演替的角度解释了肝组织形成肉芽肿的过程,即一个群落能够改变其物理环境,为生态系统的构建创造条件和资源。值得注意的是,肉芽肿是一个动态的进化系统,随着时间的推移,组成其群落的“物种”会发生渐进变化。根据生态学概念,我们不仅将肉芽肿视为细胞群落定居的地方(空间生态位或栖息地),还将其视为这些组合群体的功能活动以协调的方式发生的场所,以响应细胞因子和卵抗原等微环境梯度。最后,我们断言肉芽肿中细胞成分的组织层次如何与生态学定义的生物系统的层次结构完全吻合。通过重新思考肉芽肿作为一个整合和进化的生态系统,我们关注这个结构的内部运作,这对于理解血吸虫病至关重要,并可能指导其未来的治疗。

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