The Promise of Lung Organoids for Growth and Investigation of Pneumocystis Species.
The Promise of Lung Organoids for Growth and Investigation of Pneumocystis Species.
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DOI：
10.3389/ffunb.2021.740845
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发表时间：
2021
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肺孢子虫属（种）是宿主专性真菌寄生虫，其几乎仅在哺乳动物肺内的肺泡腔中定殖和繁殖，在那里它们可引起致命的肺炎。这种肺炎的出现在非艾滋病毒感染者引起的肺孢子虫耶氏肺孢子虫（PjP），说明了持续的重要性和需要了解其相关的病理学和开发新的治疗和预防策略。在拟定的生命周期中，肺孢子虫属。附着于肺泡1型上皮细胞（AEC 1）并阻止气体交换。这一过程中的其他机制肺孢子虫属。由于缺乏连续的离体或体外培养系统，在真实的时间内观察发病机制是具有挑战性的。本文提出的研究为小鼠肺类器官的开发提供了概念验证，这些类器官模拟表达肺泡上皮1型细胞（AEC 1）和肺泡2型上皮细胞（AEC 2）的肺泡囊。这些三维类器官的使用应有助于研究大量未回答的问题，并作为筛选新的抗PjP剂的改进手段。
Pneumocystis species (spp.) are host-obligate fungal parasites that colonize and propagate almost exclusively in the alveolar lumen within the lungs of mammals where they can cause a lethal pneumonia. The emergence of this pneumonia in non-HIV infected persons caused by Pneumocystis jirovecii (PjP), illustrates the continued importance of and the need to understand its associated pathologies and to develop new therapies and preventative strategies. In the proposed life cycle, Pneumocystis spp. attach to alveolar type 1 epithelial cells (AEC1) and prevent gas exchange. This process among other mechanisms of Pneumocystis spp. pathogenesis is challenging to observe in real time due to the absence of a continuous ex vivo or in vitro culture system. The study presented here provides a proof-of-concept for the development of murine lung organoids that mimic the lung alveolar sacs expressing alveolar epithelial type 1 cells (AEC1) and alveolar type 2 epithelial cells (AEC2). Use of these 3-dimensional organoids should facilitate studies of a multitude of unanswered questions and serve as an improved means to screen new anti- PjP agents.