The human pulmonary environment is complex, containing a matrix of cells, including fibroblasts, epithelial cells, interstitial macrophages, alveolar macrophages and neutrophils. When confronted with foreign material or invading pathogens, these cells mount a robust response. Nevertheless, many bacterial pathogens with an intracellular lifecycle stage exploit this environment for replication and survival. These include, but are not limited to, Coxiella burnetii, Legionella pneumophila, Yersinia pestis, Mycobacterium tuberculosis and Staphylococcus aureus. Currently, few human disease-relevant model systems exist for studying host–pathogen interactions during these bacterial infections in the lung. Here, we present two novel infection platforms, human alveolar macrophages (hAMs) and human precision-cut lung slices (hPCLS), along with an up-to-date synopsis of research using said models. Additionally, alternative uses for these systems in the absence of pathogen involvement are presented, such as tissue banking and further characterization of the human lung environment. Overall, hAMs and hPCLS allow novel human disease-relevant investigations that other models, such as cell lines and animal models, cannot completely provide.

中文翻译：

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让我屏住呼吸：使用原发组织模型研究病原体侵入人体肺部

人体肺部环境复杂，含有细胞基质，包括成纤维细胞、上皮细胞、间质巨噬细胞、肺泡巨噬细胞和中性粒细胞。当遇到外来物质或入侵病原体时，这些细胞会产生强烈的反应。然而，许多具有细胞内生命周期阶段的细菌病原体利用这种环境进行复制和生存。这些包括但不限于伯氏柯克氏菌、嗜肺军团菌、鼠疫耶尔森菌、结核分枝杆菌和金黄色葡萄球菌。目前，很少有人类疾病相关的模型系统用于研究肺部细菌感染期间的宿主-病原体相互作用。在这里，我们提出了两个新的感染平台，人类肺泡巨噬细胞 (hAM) 和人类精密切割肺切片 (hPCLS)，以及使用所述模型的最新研究概要。此外，还介绍了在没有病原体参与的情况下这些系统的替代用途，例如组织库和人类肺部环境的进一步表征。总体而言，hAM 和 hPCLS 允许进行其他模型（例如细胞系和动物模型）无法完全提供的与人类疾病相关的新研究。