A new tractable method for generating Human Alveolar Macrophage Like cells in vitro to study lung inflammatory processes and diseases

作者：Susanta Pahari, Eusondia Arnett, Jan Simper, Abul Azad, Israel Guerrero‐Arguero, Chengjin Ye, Hao Zhang, Hong Cai, Yu‐Feng Wang, Zhao Lai, Natalie Jarvis, Miranda Lumbreras, Diego Maselli-Caceres, Jay I. Peters, Jordi B. Torrelles, Luis Martínez‐Sobrido, Larry S. Schlesinger · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2023 · DOI：10.1101/2023.04.05.535806 · 被引用次数：10 · 研究领域：Immune cells in cancer、Phagocytosis and Immune Regulation、Extracellular vesicles in disease

ABSTRACT Alveolar macrophages (AMs) are unique lung resident cells that contact airborne pathogens and environmental particulates. The contribution of human AMs (HAM) to pulmonary diseases remains poorly understood due to difficulty in accessing them from human donors and their rapid phenotypic change during in vitro culture. Thus, there remains an unmet need for cost-effective methods for generating and/or differentiating primary cells into a HAM phenotype, particularly important for translational and clinical studies. We developed cell culture conditions that mimic the lung alveolar environment in humans using lung lipids, i.e. , Infasurf (calfactant, natural bovine surfactant) and lung-associated cytokines (GM-CSF, TGF-β, and IL-10) that facilitate the conversion of blood-obtained monocytes to an AM-Like (AML) phenotype and function in tissue culture. Similar to HAM, AML cells are particularly susceptible to both Mycobacterium tuberculosis and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. This study reveals the importance of alveolar space components in the development and maintenance of HAM phenotype and function, and provides a readily accessible model to study HAM in infectious and inflammatory disease processes, as well as therapies and vaccines. IMPORTANCE Millions die annually from respiratory disorders. Lower respiratory track gas-exchanging alveoli maintain a precarious balance between fighting invaders and minimizing tissue damage. Key p...