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

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.

Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting

“…Recently, Pahari et al demonstrated that human blood-derived monocytes cultured with lung lipids, GM-CSF, TGF-β, and IL-10 exhibited similar morphology, transcriptional profile, and functions to those of human AMs ( 148 ). While the ability to culture primary cells ex vivo is helpful, such approaches are limited by the lack of a three-dimensional environment that can mimic the cell-to-cell interaction and recapitulate the complex cellularity of the lung parenchyma and airways.…”